Search Results (749)

Background/Objectives: Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents; the survival rate is as low as 24%. Accurate prediction of clinical outcomes remains a challenge due to tumor heterogeneity and the complexity of pediatric cases. This study aims to improve predictions of progressive disease, therapy response, relapse, and survival in pediatric OS using MRI-based radiomics and machine learning methods. Methods: Pre-treatment contrast-enhanced coronal T1-weighted MR scans were collected from 63 pediatric OS patients, with an additional nine external cases used for validation. Three strategies were considered for target region segmentation (whole-tumor, tumor sampling, and bone/soft tissue) and used for MRI-based radiomics. These were then combined with clinical features to predict OS clinical outcomes. Results: The mean age of OS patients was 11.8 ± 3.5 years. Most tumors were located in the femur (65%). Osteoblastic subtype was the most common histological classification (79%). The majority of OS patients (79%) did not have evidence of metastasis at diagnosis. Progressive disease occurred in 27% of patients, 59% of patients showed adequate therapy response, 25% experienced relapse after therapy, and 30% died from OS. Classification models based on bone/soft tissue segmentation generally performed the best, with certain clinical features improving performance, especially for therapy response and mortality. The top performing classifier in each outcome achieved 0.94–1.0 validation ROC AUC and 0.63–1.0 testing ROC AUC, while those without radiomic features (RFs) generally performed suboptimally. Conclusions: This study demonstrates the strong predictive capabilities of MRI-based radiomics and multi-region segmentations for predicting clinical outcomes in pediatric OS. Full article

Nanotechnologies bring a rapid paradigm shift in hard and soft bone tissue regeneration (BTR) through unprecedented control over the nanoscale structures and chemistry of biocompatible materials to regenerate the intricate architecture and functional adaptability of bone. This review focuses on the transformative analyses and prospects of current and next-generation nanomaterials in designing bioactive bone scaffolds, emphasizing hierarchical architecture, mechanical resilience, and regenerative precision. Mainly, this review elucidated the innovative findings, new capabilities, unmet challenges, and possible future opportunities associated with biocompatible inorganic ceramics (e.g., phosphates, metallic oxides) and the United States Food and Drug Administration (USFDA) approved synthetic polymers, including their nanoscale structures. Furthermore, this review demonstrates the newly available approaches for achieving customized standard porosity, mechanical strengths, and accelerated bioactivity to construct an optimized nanomaterial-oriented scaffold. Numerous strategies including three-dimensional bioprinting, electro-spinning techniques and meticulous nanomaterials (NMs) fabrication are well established to achieve radical scientific precision in BTR engineering. The contemporary research is unceasingly decoding the pathways for spatial and temporal release of osteoinductive agents to enhance targeted therapy and prompt healing processes. Additionally, successful material design and integration of an osteoinductive and osteoconductive agents with the blend of contemporary technologies will bring radical success in this field. Furthermore, machine learning (ML) and artificial intelligence (AI) can further decode the current complexities of material design for BTR, notwithstanding the fact that these methods call for an in-depth understanding of bone composition, relationships and impacts on biochemical processes, distribution of stem cells on the matrix, and functionalization strategies of NMs for better scaffold development. Overall, this review integrated important technological progress with ethical considerations, aiming for a future where nanotechnology-facilitated bone regeneration is boosted by enhanced functionality, safety, inclusivity, and long-term environmental responsibility. Therefore, the assimilation of a specialized research design, while upholding ethical standards, will elucidate the challenge and questions we are presently encountering. Full article

Heterotopic ossification (HO) refers to the pathological formation of bone in soft tissues, typically following trauma, surgical procedures, or as a result of genetic disorders. Notably, injuries to the central nervous system significantly increase the risk of HO, a condition referred to as neurogenic HO (NHO). This review outlines the cellular and molecular mechanisms driving HO, focusing on the inflammatory response, progenitor cell reprogramming, and current treatment strategies. HO is primarily fuelled by a prolonged and dysregulated inflammatory response, characterized by sustained expression of osteoinductive cytokines secreted by M1 macrophages. These cytokines promote the aberrant differentiation of fibro-adipogenic progenitor cells (FAPs) into osteoblasts, leading to ectopic mineralization. Additional factors such as hypoxia, BMP signalling, and mechanotransduction pathways further contribute to extracellular matrix (ECM) remodelling and osteogenic reprogramming of FAPs. In the context of NHO, neuroendocrine mediators enhance ectopic bone formation by influencing both local inflammation and progenitor cell fate decisions. Current treatment options such as nonsteroidal anti-inflammatory drugs (NSAIDs), radiation therapy, and surgical excision offer limited efficacy and are associated with significant risks. Novel therapeutic strategies targeting inflammation, neuropeptide signalling, and calcium metabolism may offer more effective approaches to preventing or mitigating HO progression. Full article

Background: Soft tissue sarcomas (STSs) are a rare and heterogeneous group of mesenchymal tumors with limited response to current therapies, particularly in advanced stages. STS tumors were traditionally considered “cold” tumors, characterized by limited immune infiltration and low immunogenicity. However, emerging evidence is challenging this perception, highlighting a potentially critical role for the immune system in STS biology. Objective: Building on our previous findings suggesting impaired natural killer (NK) cell activity in STS patients, we aimed to perform an in-depth characterization of peripheral NK cells in STS. Methods: Peripheral blood samples from STS patients and sex- and age-matched healthy donors were analyzed to assess NK cell degranulation, IFNγ production, and receptor repertoire. Results: Functional assays revealed a notable reduction in both degranulation and IFNγ production in NK cells from STS patients. STS patients also exhibited dysregulated expression of activating and inhibitory NK cell receptors. Principal component analysis (PCA) identified CD27 and NKp44 as critical markers for distinguishing STS patients from healthy donors. Increased CD27 expression represents a shift towards a more regulatory NK cell phenotype, and we found that CD27 expression was negatively correlated with NK cell degranulation and IFNγ production. ROC curve analysis demonstrated strong potential to distinguish between the groups for both CD27 (AUC = 0.85) and NKp44 (AUC = 0.94). Conclusion: In conclusion, STS patients exhibited impaired NK cell function, altered receptor repertoire, and a shift towards a less cytotoxic and more regulatory phenotype. Full article

Introduction/Objectives: Osteoarthritis (OA) is a chronic systemic disease that affects the entire array of joint structures. It is one of the most common chronic, socially significant diseases, associated with a decline in the quality of life of patients and constantly increasing the cost of treatment. Clinical trial outcomes are largely inconclusive, and OA remains one of the few musculoskeletal diseases without an established disease-modifying therapy. One potential explanation is the use of ineffective tools for OA classification, patient stratification, and the assessment of disease progression. There is growing interest in musculoskeletal ultrasonography (MSK US), as it enables the dynamic visualization of the examined structures and gives information about both inflammatory and structural changes that have occurred. Determining the leading ultrasound phenotype, which depends on the most damaged tissue at a given time (bone, cartilage, synovial membrane, joint capsule, ligaments, tendons, menisci, etc.), can rationalize therapy use by selecting patients more suitable for specific treatments. This article aims to evaluate and summarize the potential of MSK US in the process of determining the clinical phenotype of OA and to emphasize the importance of this imaging modality in evaluating further therapeutic strategies. Method: A single-center prospective study conducted in the period of September 2023–June 2024 enrolled 259 consecutive patients with proven OA. The statistical program Minitab version 22.2.1 (2025) was used to analyze the data. The predominant and secondary phenotypes were tabulated for each OA localization and were presented numerically and as relative proportions (%). The rate of the most frequently occurring phenotypes was compared against that of the less frequent ones through paired z-tests. The initially acceptable type I error was set at 5%; it was further adjusted for the number of comparisons (Bonferroni). Results: The most frequent and predominant US phenotype for patients with knee OA was intra-articular effusion (n = 47, 37.90%). It was significantly higher compared to the rest of the US phenotypes: synovial proliferation (n = 22, 17.70%; p < 0.001), cartilage destruction (n = 26, 21%; p = 0.001), altered subchondral bone (n = 8, 6.50%; p < 0.001), extra-articular soft tissue changes (n = 12, 9.70%; p < 0.001), crystal deposits (n = 6, 4.8%; p < 0.001), and post-traumatic (n = 3, 2.40%; p < 0.001). The most common US phenotype for hip OA was altered subchondral bone (n = 32, 47.1%), with significant differences from intra-articular effusion (n = 12, 17.60%; p = 0.001), synovial proliferation (n = 5, 7.40; p = 0.001), cartilage destruction (n = 12, 17.60%; p = 0.001), extra-articular soft tissue changes (n = 3, 4.40%; p = 0.001), crystal deposits (n = 3, 4.40%; p = 0.001), and post-traumatic (n = 0). Altered subchondral bone was also the leading US phenotype for hand OA (n = 31, 55.40%), with significant differences compared to intra-articular effusion (n = 1, 1.80%; p < 0.001), synovial proliferation (n = 7, 12.50%; p < 0.001), cartilage destruction (n = 11, 19.60%; p < 0.001), extra-articular soft tissue changes (n = 2, 3.60%; p < 0.001), crystal deposits (n = 3, 5.40%; p < 0.001), and post-traumatic (n = 1, 1.80%, p < 0.001). For shoulder OA, extra-articular soft tissue changes were the most frequent (n = 8, 46.20%), followed by post-traumatic (n = 4, 30.70%), as the rate of both phenotypes was significantly higher compared to that of intra-articular effusion (n = 0), synovial proliferation (n = 0), cartilage destruction (n = 1, 7.70%; p = 0.003), and crystal deposits (n = 0). Conclusions: The therapeutic approach for OA is a dynamic and intricate process, for which the type of affected joint and the underlying pathogenetic mechanism at a specific stage of the disease’s evolution is essential. MSK US is one of the options for the clinical phenotyping of OA. Some of the suggested ultrasound subtypes may serve as the rationale for selecting a particular treatment. Full article

Peri-implantitis is an inflammatory disease-causing bone loss around dental implants, often requiring reconstructive surgical therapies to reduce probing depth and regenerate bone. However, such surgeries are frequently complicated by postoperative issues. This retrospective case series aimed to identify the main postoperative complications following the reconstructive treatment of peri-implant bone defects in peri-implantitis patients. Data from 14 patients with 21 affected implants were analyzed, including demographics, oral hygiene, surgical techniques, and complications such as wound dehiscence, membrane exposure, and infections. Wound dehiscence was measured using Image J^® software version 1.54. Descriptive and bivariate analyses were performed. The results showed that 11 implants (52.4%; 95% confidence interval (95%CI): 29% to 76%) in nine patients (57.1%; 95%CI = 27% to 87%) developed soft tissue dehiscence after one week, with membrane exposure observed in 4 implants. Dehiscence was significantly associated with mandibular implant location (p = 0.003), poor interproximal hygiene (p = 0.008), and membrane exposure (p = 0.034). No postoperative infections were recorded. In conclusion, more than half of peri-implantitis patients undergoing reconstructive surgery experience wound dehiscence, particularly in cases involving mandible, poor hygiene, and membrane exposure. This complication might compromise bone regeneration and reduce the treatment success rate. These results should be interpreted cautiously due to study design limitations (retrospective design, lack of a control group, and small sample size). Full article

Sarcomas are heterogeneous mesenchymal tumors, and their pharmacological treatment remains challenging due to the high toxicity and poor efficacy of current therapies. This study aimed to identify common overexpressed kinases in the four most frequent sarcoma subtypes to establish novel therapeutic targets. A bioinformatics approach using patient-derived gene expression data sets identified overexpressed kinases shared across these sarcoma types. Later, BUB1 was determined as the kinase consistently overexpressed across the osteosarcoma, liposarcoma, leiomyosarcoma, and synovial sarcoma. Moreover, the role of this kinase was further validated through molecular and functional assays, including pharmacological inhibition in cell lines derived from the four sarcoma subtypes. BUB1 inhibition reduced the phosphorylation of AKT and H2A proteins, precluded cell proliferation, and inhibited colony formation in sarcoma cells. Finally, overall survival analysis highlighted a strong correlation between high BUB1 expression and poorer survival rates in sarcoma patients. Altogether, these findings underscore the potential of BUB1 as a therapeutic target and prognostic marker in sarcomas. Targeted inhibition of BUB1 may provide a novel strategy to reduce tumor growth and improve outcomes for patients with bone and soft tissue sarcomas. Full article

Background: Surface electromyography (sEMG) enables the non-invasive assessment of muscle activity and is widely used in orthodontics for evaluating masticatory muscles. However, little is known about the dynamic changes in facial expression muscles during orthodontic treatment. This study aimed to investigate alterations in facial muscle tone during the leveling and alignment phase in adult female patients undergoing fixed appliance therapy. Methods: The study included 30 female patients aged 20–31 years who underwent sEMG assessment at four time points: before treatment initiation (T0), at the start of appliance placement (T1), three months into treatment (T2), and six months into treatment (T3). Muscle activity was recorded during four standardized facial expressions: eye closure, nasal strain, broad smile, and lip protrusion. Electrodes were placed on the orbicularis oris, orbicularis oculi, zygomaticus major, and levator labii superioris alaeque nasi muscles. A total of 1440 measurements were analyzed using Friedman and Conover-Inman tests (α = 0.05). Results: Significant changes in muscle tone were observed during treatment. During lip protrusion, the orbicularis oris and zygomaticus major showed significant increases in peak and minimum activity (p < 0.01). Eye closure was associated with altered orbicularis oris activation bilaterally at T3 (p < 0.01). Nasal strain induced significant changes in zygomaticus and levator labii muscle tone, particularly on the right side (p < 0.05). No significant changes were noted during broad smiling. Conclusions: Orthodontic leveling and alignment influence the activity of selected facial expression muscles, demonstrating a dynamic neuromuscular adaptation during treatment. These findings highlight the importance of considering soft tissue responses in orthodontic biomechanics and suggest potential implications for facial esthetics and muscle function monitoring. Full article

Doxorubicin (DOX) is a highly effective chemotherapy drug used in the treatment of many cancers, including solid tumors, hematological malignancies, and soft tissue sarcomas. Despite its potent antitumor effects, DOX is known to have toxic effects in non-tumorous tissues, such as skeletal muscle. Potential mediators of DOX-induced skeletal muscle toxicity are reactive oxygen species (ROS). An overproduction of ROS can disrupt the balance between oxidants and antioxidants in a cell, leading to oxidative stress. Chronic oxidative stress has been shown to upregulate proteolysis, ultimately leading to muscle wasting. Exercise stands as a potent nonpharmacological therapy capable of attenuating muscle wasting by enhancing metabolic function and antioxidant defenses while suppressing harmful ROS production. This review focuses on the current understanding of the role of oxidative stress in DOX-induced skeletal muscle toxicity. In addition, we highlight the effects of various exercise types on oxidative stress and muscle remodeling during DOX chemotherapy. Full article

Background/Objective: Laser therapy has gained attention in dental practice to minimize bleeding and enhance blood clot formation. This study aimed to explore the utilization and to compare the clinical efficacy of laser-mediated hemostasis for older patients receiving routine dental treatment. Methods: A prospective observational study was conducted across research networks between October 2023 and August 2024, involving 60 patients aged 50 years and older (average = 63.35 years) at risk of postoperative bleeding following dental treatments. Additionally, laser therapy for hemostasis was selected and provided among calibrated operators. A single researcher performed data collection. Before statistical analysis, data verification and clinical assessment were conducted by the operators and researcher. A clinical cut-off for hemostasis was set at 5 min. Two diode laser machines were used namely, an 810 nm and dual wavelengths of 635 nm and 980 nm. Results: There were 94 extraction sockets, 28 procedures of scaling and root planing and 18 procedures of minor oral surgery. Combining laser ablating sulcular fiber and photobiomodulation initiating blood clot formation was a preferable hemostatic technique for extraction socket, while photobiomodulation alone was a preferred technique for soft tissue hemostasis (p < 0.001). All operators confirmed that 97.86 percent of bleeding events achieved more rapid hemostasis. 61.43 percent of bleeding events clinically achieved hemostasis within 5 min by using laser-mediated hemostasis alone (p = 0.092). Full recovery of the extraction socket was significantly observed during the 2- to 4-week follow-up period (p = 0.005). No clinical complications were reported. Conclusions: Laser-mediated hemostasis effectively reduced hemostatic duration, prevented postoperative bleeding and promoted wound healing in older patients undergoing routine dental treatment. Full article

Malignant peripheral nerve sheath tumors (MPNSTs) are a rare type of soft tissue sarcoma associated with poor prognoses. The standard of care for non-resectable tumors consists of surgical excision followed by radiation and chemotherapy. MPNSTs are most common in patients with neurofibromatosis type 1 but can also occur sporadically. Regardless of origin, MPNSTs most often rely on signaling pathways that increase basal oxidative stress. This provides the basis for developing therapeutics with mechanisms that can potentiate oxidative stress to selectively eradicate tumor cells at doses that are tolerable for normal cells. Artemisinin derivatives are a mainstay of malaria therapy worldwide, with a well-established safety profile. Artemisinin’s antimalarial effects are due to an endoperoxide bridge in its chemical structure that induces oxidative stress. We found that artesunate (ARS) and metabolite dihydroartemisinin (DHA) are selectively cytotoxic to MPNST cells relative to normal Schwann cells with the endoperoxide bridge required for activity. Mechanistically, DHA induced oxidative stress, lipid peroxidation, and DHA-mediated cytotoxicity could be prevented with co-administration of the antioxidant N-acetyl-cysteine. Furthermore, we found that DHA was able to selectively remove MPNST from co-culture with normal Schwann cells. These data supports the further development of artemisinins for the clinical management of MPNST. Full article

Background: Klippel–Trenaunay syndrome (KTS) is a congenital vascular malformation syndrome characterized by low-flow vascular anomalies, including venous malformation (VM) and lymphatic involvement. These anomalies may lead to limb asymmetry due to soft tissue and/or bone overgrowth. Compression therapy using elastic garments is considered a conservative and minimally invasive first-line treatment option for KTS. However, the benefits of compression therapy for low-flow vascular malformations, particularly limb VMs, have not been sufficiently evaluated. This prospective, multi-center study assessed the efficacy and safety of compression therapy for KTS with VM. Methods: After measuring the affected limb, a custom-made elastic garment providing 30 mmHg of compression was manufactured (THUASNE, France). A total of 20 patients (7 male, 13 female; mean age: 10.9 years) underwent compression therapy for 26 weeks at four nationwide institutions in Japan. The primary outcome was the change in lower limb circumference. Secondary outcomes included pain, modified Rankin Scale (mRS) score, body water content, vital signs, changes in garment elasticity, and adverse events. Results: All 20 patients completed the study. At the study endpoint, the circumference ratio of the affected to unaffected limbs was significantly reduced at the superior end of the tibial tuberosity (p = 0.02) and the thinnest part of the ankle (p < 0.001). The elastic force of the garment declined by approximately 50% over 26 weeks. No serious adverse events related to the intervention were reported. Conclusions: Compression therapy using a custom-made elastic garment appears to be a safe and effective approach for managing limb overgrowth in patients with KTS and VM. To maintain the therapeutic effect, garment replacement is recommended at least every six months. Full article

Background/Objectives: The variety of magnetic resonance imaging (MRI) scales available to measure soft tissue and osteochondral changes in joints of persons with hemophilia poses challenges in evaluating published clinical/research studies. To evaluate the value of four MRI scales [(i) the 17-point International Prophylaxis Study Group [IPSG] additive scale; (ii) and (iii) the compatible IPSG progressive (P) and additive (A) scales; and (iv) the Denver progressive scale] to assess joint change in boys with hemophilia participating in a prospective two-year prophylaxis study. Methods: Boys with severe hemophilia A (ages, 7–16 years) followed at the Hospital for Sick Children, Toronto, Canada had MRI evaluations of six index joints (ankles, knees, elbows) at study entry and exit. Musculoskeletal (MSK) outcomes included in the study were the Colorado Child Physical Examination (PE) scale; the Pettersson (X-ray) scale; and the aforementioned 4 MRI scales. Results: Very strong (r ≥ 0.80) correlations were observed between the IPSG 17-point, the IPSG progressive (P) and the Denver MRI scales, and moderate (r = 0.40–0.59) to strong (r = 0.60–0.79) correlations for the IPSG 17 point and the IPSG additive (A) MRI scales. Very weak (r = 0.20–0.39) or no correlations were observed between soft tissue MRI scores and the swelling item of the Child PE scale. Conclusions: All four MRI scales demonstrated relative comparability of their construct validities for assessing mild/moderate hemophilic arthropathy. The 17-point IPSG additive scale is recommended as a reference standard in future long-term studies of young boys with hemophilia receiving factor and non-factor-based preventive therapies. Full article

Skin and soft tissue infections (SSTIs) are becoming an urgent public health issue worldwide. The globe is facing a growing problem with drug-resistant germs, and current treatments are not quite cutting it. There is a real need for new therapies that can tackle these challenges more effectively. This brings us to an interesting question: Can extracellular vesicles (EVs) from different sources, such as mesenchymal stem cells (MSCs), immune cells, or even plants and animals, help in treating SSTIs, especially given the rise in drug resistance? Studies have shown that MSC-derived EVs are particularly noteworthy because they carry components such as antimicrobial peptides (AMPs) that can work together to fight infections, boost the immune response, and aid in healing. These vesicles play a role in how our body interacts with infections, helping to clear bacteria, reduce inflammation, and promote tissue repair. We also see that EVs from plants and bacteria can directly fight off germs, while those from animals can support the healing process of skin. Although early studies have shown promise for EV therapies, there are still hurdles to overcome, such as ensuring consistent production and delivery. This review looks at the potential of EVs as powerful agents in managing infections and supporting healing, highlighting an exciting area of research in medicine. Full article

This study aimed to evaluate the impact of Twin Block appliance therapy on skeletal, dentoalveolar, and facial soft tissue characteristics. The study included 18 participants with Class II skeletal malocclusion who were treated with the Twin Block appliance. Lateral cephalograms and 3D face scans were analyzed before and after therapy for each participant. Dependent t-test results showed a significant increase in the protrusion of the lower incisors (p < 0.001), proclination of the lower incisors (p = 0.021), SNB (p = 0.005), Ls:E (p = 0.040), mandibular length (p < 0.001), and soft tissue mandible length (p < 0.001) and a significant decrease in the ANB (p = 0.003), Wits (p = 0.001), ANPG (p = 0.001), overbite (p = 0.001), and the retrusion of upper incisors (p = 0.002). Twin Block therapy caused changes in skeletal and soft tissue characteristics. The increase in the SNB angle and mandibular length, accompanied by the decrease in the ANB and Wits values reduced the skeletal discrepancy. The reduction in the ANPG indicated an improvement in the skeletal profile. Additionally, the increase in the soft tissue mandible length and distance between the upper lip and E-line contributed to improved esthetic soft tissue profile characteristics. Full article