Search Results (41,027)

Background/Objectives: Traumatic dental injuries involving the maxillary anterior teeth are common; however, combined extrusive and lateral dislocation during active orthodontic treatment is uncommon and presents unique management challenges. This case report describes the multidisciplinary management of traumatic extrusive and lateral dislocation of the maxillary right lateral incisor (#7) and maxillary right central incisor (#8) in a 27-year-old patient undergoing fixed orthodontic treatment following sports-related trauma. Methods: Clinical examination revealed marked coronal and lateral displacement, pathologic mobility, gingival laceration, active bleeding, and deformation of the orthodontic archwire. Both affected teeth had complete root formation. Emergency management included immediate repositioning of the displaced teeth and urgent endodontic treatment. Semi-rigid stabilization was achieved using metallic ligatures and a rectangular stainless-steel orthodontic archwire, supplemented by temporary skeletal anchorage with a mini-screw and posterior bite turbos to reduce occlusal loading. The patient was monitored clinically and radiographically throughout healing and subsequent orthodontic treatment. Results: Follow-up examinations demonstrated favorable periodontal healing, stable retention of the traumatized teeth, absence of pathologic mobility, and successful continuation of orthodontic treatment. Radiographic evaluation showed no evidence of inflammatory root resorption or other significant complications. At the 16-month follow-up, the affected teeth remained functional and stable, and implant placement was successfully completed at the congenitally missing maxillary canine site. Conclusions: This case highlights the importance of immediate interdisciplinary management of traumatic dental dislocation during orthodontic treatment. Fixed orthodontic appliances, when appropriately incorporated into emergency stabilization protocols, may contribute to successful tooth retention and favorable long-term outcomes. Full article

Over the past decade, the use of nanomaterials and nanomedical devices has been increasingly explored for cancer treatment. Although the outcomes of conventional therapies have improved patient survival, these approaches still present important limitations for some types of cancer and metastasis. Challenges such as poor drug accumulation in solid tumors and lack of specificity and selectivity can be addressed through alternative nanomedicine-based treatments. Among the wide range of nanoplatforms whose composition and shape have been designed for cancer treatment, this review focuses specifically on those based on natural proteins, including advanced carriers and engineered proteins bearing active targeting and/or therapeutic agents. The objective of this review is to provide a comparative and translational analysis of protein-based nanomaterials for cancer therapy, highlighting their unique characteristics, such as biocompatibility, biodegradability, and the ability to integrate bioactive peptides that can trigger or respond to tumor-specific or altered physiological stimuli. Several protein-based nanomedical devices have been developed for theranostic applications, demonstrating enhanced performance in tumor imaging and cancer treatment. This review introduces a structured analytical framework that classifies protein-based nanomaterials according to their biological origin, functional design, and clinical readiness, enabling systematic evaluation across platforms. Rather than providing a descriptive overview, this work offers a structured comparative analysis of protein-based nanomaterials, highlighting design trade-offs, translational challenges, and factors influencing clinical applicability. Full article

Bladder cancer is the fifth most common cancer in the United States, causing approximately 17,000 deaths annually. Due to its vast genetic and molecular heterogeneity, presentation, prognosis, and therapeutic response vary greatly between individuals. To improve patient outcomes, there is a need for better drug-screening platforms. The genetic heterogeneity of bladder cancer often leads to chemotherapy resistance or low response rates. Moreover, chemotherapies are often contraindicated in patients with select comorbidities. Organoids offer a better option to replicate the tumor microenvironment than traditional 2D cell cultures, improving drug development and personalized therapy. In this study, we bioprinted gelatin-methacrylol (GelMA)-based organoids containing bladder cancer cell lines of different grades to model muscle-invasive bladder cancer. In the organoids, we observed distinct grade-dependent tumor proliferation and progression dynamics. Treatment with standard-of-care chemotherapies revealed a grade-dependent tumor response consistent with in vivo patient data, highlighting the suitability of these organoids for rapid, reliable drug testing. Lastly, we used the organoids to test LCI139, a novel small-molecule inhibitor of PI3K, CDK4/6, and CDK9 designed for the treatment of epithelial cancers, underscoring the potential of our model to evaluate the efficacy of newly developed drugs. The ability to quickly biofabricate reproducible bladder cancer organoids that are adaptable to different tumor grades represents a novel strategy to create an in vitro platform with strong potential to predict treatment outcomes of bladder cancer patients. Full article

Ubiquitination is a post-translational modification that governs various facets of eukaryotic biology, including protein stability, signaling, and immune regulation. The modification process is mediated by a coordinated enzymatic cascade, in which E3 ubiquitin ligases confer substrate specificity and determine the functional outcome of ubiquitin attachment. In the case of a virus infection, host cellular signaling networks undergo major ubiquitin-dependent changes to protect the host cell, including remodeling of cellular organelles, coordination of innate immunity, and reprogramming of metabolic pathways to prevent virus replication. African swine fever virus (ASFV) has evolved numerous strategies to counteract or evade these responses, thereby manipulating host defenses and promoting its replication. By modulating ubiquitination-dependent host cellular functions, the virus can regulate key immune signaling factors, suppress interferon production, and interfere with inflammatory pathways. These actions not only antagonize antiviral defenses but also remodel cellular homeostasis to favor infection. The important interplay between host defense and viral manipulation underscores the versatility of the ubiquitin system as a battleground in ASFV infection. In this review, we discussed mechanistic insights into how ASFV subverts ubiquitin pathways during host–virus interactions. This comprehensive knowledge might be beneficial for pharmaceutical exploration of host E3 ligase-dependent anti-ASFV treatment. Full article

Treatment of cleft lip alveolus and/or palate includes surgical repair to treat communication-related outcomes such as velopharyngeal insufficiency and otological dysfunction. Robot-assisted surgery has recently evolved into a promising adjunct to conventional surgery, particularly for complex procedures such as transoral (reconstructive) surgery. This structured literature review aims to investigate whether robot-assisted transoral cleft palate repair enhances communication (i.e., speech and otological) outcomes compared to conventional manual cleft palate surgery. A literature search was performed using PubMed, Embase, the Cochrane Library and Google Scholar. Primary outcomes were the change in cleft speech characteristics and otological disease after robot-assisted cleft palate surgery versus manual cleft palate surgery. The available evidence on communication-related outcomes remains sparse. Six relevant articles were included. In only one study, transoral robotic cleft surgery (TORCS) significantly reduced otitis media with effusion (OME), need for ventilation tubes and hearing threshold within 2 years post-surgery. No postoperative speech or velopharyngeal outcomes were reported. In conclusion, transoral robotic cleft surgery (TORCS) appears safe and feasible for repair of a cleft palate. It provides superior intraoral view and improved surgeon ergonomics. Current drawbacks are the costs and the available tools, the extended surgical duration and the lack of haptic feedback, which limit the current clinical applicability of TORCS. Based on limited clinical evidence, TORCS may support faster recovery of Eustachian tube function and hearing, but no conclusions on speech outcomes can yet be drawn. Full article

Biochar can improve soil physicochemical properties and microbial habitats; however, its application rate-dependent effects in maize fields of the black soil region remain insufficiently understood under field conditions. A three-year field experiment was conducted in Jiamusi, Heilongjiang Province, China, from 2023 to 2025, with four biochar application rates: 0 (W0), 10 (W1), 20 (W2), and 40 t ha⁻¹ (W3). Soil physicochemical properties, bacterial communities based on 16S rRNA gene sequencing, and fungal communities based on internal transcribed spacer (ITS) sequencing were analyzed to assess changes in soil fertility and microbial community composition and their relationships with environmental factors. Biochar application significantly increased soil organic matter, alkali-hydrolyzable nitrogen, available potassium, and pH. Although W3 produced the greatest nutrient enhancement, W2 exhibited a more balanced overall response across the measured soil fertility and microbial community indicators. Sequencing depth was adequate for all samples, and bacterial alpha diversity was comparatively well maintained under W2 and W3. Fungal alpha diversity exhibited pronounced interannual variation and increased under W3 in 2025. Year accounted for a greater proportion of variation in microbial community structure than did biochar treatment; however, both treatment and the year × treatment interaction also had significant effects. Among the measured soil fertility and microbial community indicators, W2 produced a comparatively balanced overall response, whereas W3 exerted stronger selective effects on microbial communities. Because crop yield, economic feasibility, labile carbon fractions, and long-term ecological outcomes were not assessed, an agronomically optimal biochar application rate cannot yet be determined. Full article

Blood-based biomarkers have emerged as promising, minimally invasive tools for the diagnosis, prognostic stratification, and treatment monitoring of non-small cell lung cancer (NSCLC), including markers of tumor burden, tumor dissemination, immune signaling, and post-transcriptional regulation. However, evidence across biomarker classes remains fragmented. This study aimed to synthesize published evidence on major blood-based biomarkers relevant to diagnosis, prognosis, treatment stratification, and monitoring in NSCLC. PubMed was searched for systematic reviews and meta-analyses of blood-based biomarkers in NSCLC. Of 356 screened records, 82 underwent full-text review, and 57 systematic reviews/meta-analyses were included. Biomarkers were grouped into four categories: circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), cytokines/soluble immune proteins, and non-coding RNAs (ncRNAs). Reported pooled effect estimates were extracted by biomarker class and evidence domain, and the methodological quality of included reviews was assessed using AMSTAR 2. Evidence was unevenly distributed across biomarker classes and evidence domains. Circulating ncRNAs were mainly represented in diagnostic and prognostic evidence; selected diagnostic ncRNAs, including miR-145, miR-25, and circRNAs, showed reported AUCs ranging from 0.83 to 0.85. ctDNA was represented across diagnostic, prognostic, treatment-stratification, and dynamic monitoring evidence, with ctDNA positivity associated with poorer survival or recurrence outcomes and ctDNA clearance or decline associated with improved outcomes. CTC evidence was primarily prognostic, with CTC positivity associated with worse overall survival and disease-free survival. Soluble immune biomarker evidence was also primarily prognostic, with elevated soluble PD-L1 and IL-6 associated with adverse survival outcomes and limited exploratory monitoring evidence for exosomal PD-L1. Overall, the evidence suggested distinct but complementary roles across biomarker classes, although direct head-to-head comparisons were lacking. Blood-based biomarkers show potential to support diagnosis, prognosis, and longitudinal monitoring in NSCLC, but their reported utility differs by biomarker class and clinical context. In the available review-level evidence, ncRNAs were mainly represented in diagnostic and prognostic evidence, while ctDNA was represented across diagnostic, prognostic, treatment-stratification, and dynamic monitoring evidence. CTCs were mainly represented in prognostic evidence, and soluble immune biomarkers were primarily represented in prognostic evidence, with limited exploratory evidence for dynamic monitoring. Further assay standardization, prospective validation, and direct comparative studies are needed before these biomarkers can be routinely integrated into clinical practice. Full article

Background: The Codubix^® ŻEBRA and Codubix^® S ŻEBRA prostheses (by Tricomed SA), made of a biocompatible polypropylene–polyester braid, were developed as tools for the treatment of bone defects resulting from cancer surgery or mechanical injuries. Methods: The retrospective analysis investigation presents the efficacy and safety of rib bone prostheses made of knitted polyester–polypropylene fabric used to fill defects in the ribs and sternum. Data were collected from 113 patients (68 males, 45 females) undergoing surgery at three clinical centres. Prosthesis implantation was performed to bridge bone defects in the ribs and/or sternum. The analysis included preoperative and intraoperative data, two follow-up visits and a final interview with the patients. All prostheses were implanted using two techniques for filling defects in the chest wall: the ‘hammock’ (suspension) fixation method in 87 patients, and the ‘rigid’ fixation method in 26 patients. Results: The main cause of defects was cancer surgery (95.6%) performed in cases of sarcomas, squamous cell carcinomas, and desmoid tumours. Other causes (e.g., congenital defects and mechanical trauma) were less common. The ‘rigid’ fixation method extended the surgery time by approximately 16 min compared to the suspension method. Differences were also noted in the recovery period—an average of 56 days for the ‘hammock’ method and 30 days for the ‘rigid’ method. During the second follow-up visit, the treatment outcome using these prostheses was rated as good in 90.3% of cases. The average duration of hospitalisation was 21 days, regardless of the implantation method. No prosthesis-related adverse events were reported. Complications were observed in 21 cases in the first days after surgery. The most common ones were sensory disturbances (5.3%), infections (3.5%), haematomas and blood effusions (2.7%). Conclusions: A retrospective study demonstrates that knitted prostheses are safe and effective solution for repairing extensive defects resulting from tumours, trauma or congenital malformations. The implants ensure high patient comfort and maintain normal physical functioning without interference. Full article

Background/Objectives: A recent Delphi survey of endocrinologists revealed low consensus regarding the diagnosis of pediatric growth hormone deficiency (GHD). Thus, we sought to describe the various trajectories undertaken by healthy 8–14-year-old youth in the 2 years following testing for GHD at a single major pediatric academic institution. Methods: Electronic health records were reviewed for the current analysis from healthy 8–14-year-old participants enrolled in a prospective longitudinal observational study of parent and youth characteristics associated with youth quality of life and self-esteem over a two-year period following growth hormone (GH) stimulation testing. Participants were grouped according to their peak GH concentration on testing (<7, 7–10, and ≥10 ng/mL), and outcomes included treatment (or not) with GH or other growth-altering hormonal treatments. Results: Of the 115 participants, 27 (23%) had peak GH < 7 ng/mL, 27 (23%) 7–10 ng/mL, and 61 (53%) peaked ≥ 10 ng/mL. Across the three groups, some patients were not offered GH treatment, some were offered yet did not pursue treatment, and some were offered and treated—with further variance provided by GH treatment interruptions, early cessation vs. continued GH treatment, delayed GH treatment start, and treatment with other agents (testosterone, gonadotropin-releasing hormone agonist, or aromatase inhibitor) either in lieu of or in addition to GH. Conclusions: Even within the network of a single academic institution, variability is evident in the management of healthy 8–14-year-old short youth following GH stimulation testing. Full article

Hypomethylating agents (HMAs) are the cornerstone in the treatment of higher-risk myelodysplastic syndromes (MDSs), particularly for patients who are not candidates for allogeneic hematopoietic cell transplant (allo-HCT). Despite demonstrated efficacy in improving hematologic outcomes, the clinical management of HMA-associated myelosuppression remains a challenge. This review discusses the use of azacitidine and oral decitabine-cedazuridine (DEC-C) for MDS management in the Canadian context, with a focus on optimizing therapy to mitigate myelosuppression and prevent early HMA discontinuation due to toxicity. Close monitoring of complete blood counts is critical to early detection of myelosuppression and management of treatment-related cytopenias. In the real-world setting, specific HMA dose adjustments are used based on patient risk factors for myelosuppression or treatment-related complications. Supportive care strategies, including the use of growth factors and antimicrobials, can complement monitoring and dose modifications for HMA-related myelosuppression management, although their use is variable. This review summarizes current evidence and real-world management approaches for HMA-induced myelosuppression, with the aim of improving outcomes for patients undergoing treatment for MDS. Full article

Circulating tumor DNA fraction (ctFraction) has emerged as an important biomarker for assessing tumor burden and monitoring treatment response in patients with cancer. In this study, we compared ctFraction estimates generated by ichorCNA, Fragle low-pass whole-genome sequencing (Fragle LP-WGS), Fragle off-target, and OTTER, a proprietary algorithm from Tempus AI. Plasma samples from 33 patients with advanced solid tumors were analyzed using a ctDNA assay targeting 150 cancer-associated genes, and ctFraction estimates generated by the different methods were compared. Fragle off-target demonstrated the highest concordance with Fragle LP-WGS (rho = 0.903), followed by OTTER (rho = 0.698) and ichorCNA (rho = 0.696), while OTTER and ichorCNA showed strong agreement (rho = 0.826). Mean VAF (mVAF) significantly correlated with all ctFraction estimates, with the strongest association observed for ichorCNA (rho = 0.910), followed by OTTER (rho = 0.865), Fragle LP-WGS (rho = 0.680), and Fragle off-target (rho = 0.658). Longitudinal analysis of 20 patients at baseline and after two cycles of treatment demonstrated strong correlations between changes in ctFraction (ΔctFraction) and mean ΔVAF for both ichorCNA and Fragle off-target (r = 0.955 and r = 0.906, respectively). Overall, these findings demonstrate that ctFraction estimates derived from copy-number- and fragmentomic-based approaches show strong concordance across advanced solid tumors and significantly correlate with mVAF, a commonly used measure of ctDNA abundance. Fragle off-target, in particular, provides an efficient strategy for ctFraction estimation directly from existing targeted sequencing data, eliminating the need for additional sequencing. Larger prospective studies are warranted to further evaluate Fragle off-target clinical utility for treatment monitoring and outcome prediction. Full article

Valproic acid (VPA) is a human developmental toxicant that causes neural tube defects and neurobehavioral deficits. Recent work has implicated VPA-induced oxidative stress in cell models of neurodifferentiation, where oxidative post-translational modifications (PTMs) in undifferentiated cells, primarily protein sulfenylation (Pr-SOH), were unique compared to differentiated neurons, primarily protein S-glutathionylation (Pr-SSG). Many of these effects could be mitigated by pretreatments with an Nrf2 inducer. However, it is unclear how early-stage mouse embryos (gestational day 8.5) respond to VPA treatments. Using whole embryo culture, mouse embryos were treated with VPA. A time course assessment of glutathione/glutathione disulfide redox potentials was performed via HPLC throughout 24 h of culture. At 6 h of VPA treatment, embryos were collected for the assessment of protein redox states and specific protein PTMs via various blotting techniques. Also, at 6 h of treatment, the localization of specific PTMs was determined via whole mount staining. Some embryos were pretreated with an Nrf2 inducer. Our data demonstrated that VPA caused a sharp oxidation of redox potentials, which were the greatest between 2 and 6 h, but reverted to control levels by 24 h. Preemptive Nrf2 activation prevented VPA-induced oxidation. Redox blotting showed that VPA caused oxidation of the proteome but this could be reversed by D3T pretreatment. More specifically, Pr-SOH levels increased but Pr-SSG levels were unchanged. Increased Pr-SOH could also be reversed with prior Nrf2 activation. We conclude that embryos at these early stages of development are highly sensitive to VPA and respond more like undifferentiated cells, promoting a more pro-oxidizing outcome for proteins, increasing Pr-SOH formation vs. Pr-SSG. These findings may support specific windows of development where embryos are more susceptible to VPA-induced oxidative injury. Further understanding of redox control and regulation at these susceptible states may serve to develop preventative strategies to reduce poor developmental outcomes after exposures. Full article

Introduction: Isolated peroneus longus (PL) tendon tears are rare injuries and an often-overlooked cause of chronic lateral ankle pain. Evidence regarding optimal conservative management, especially in elite athletes, remains limited. Focused extracorporeal shockwave therapy (F-ESWT) has shown promising results in tendinopathies, yet its application in acute tendon tears is poorly documented. Methods: We present the case of a professional football player in his late twenties who sustained an isolated longitudinal PL tear. The player underwent a combined conservative protocol including F-ESWT, physiotherapy, and custom orthotics. Pain (Visual Analog Scale, VAS) and function (AOFAS Ankle–Hindfoot Score) were assessed at baseline, three months, and in an 18-month follow-up. MRI scans were obtained at diagnosis and after six weeks to evaluate tendon healing. Results: The conservative treatment protocol, including eight sessions of ultrasound-guided F-ESWT (2500–4000 impulses per session, 50–550 µJ/mm²) led to marked pain relief and functional improvement. VAS decreased from 7/10 to 1/10, while AOFAS improved from 57 to 95 points, maintained at 18 months. MRI after six weeks of treatment demonstrated decreased intratendinous hyperintensity, reduced lesion length, and re-establishment of normal tendon architecture. The player returned to training after eight weeks and full competition after 12 weeks, remaining asymptomatic thereafter. Conclusions: A multimodal treatment consisting of F-ESWT, physiotherapy with progressive loading and orthotic correction resulted in rapid and durable healing of an isolated PL tear in a professional athlete. This case supports the potential role of a multimodal conservative treatment strategy including F-ESWT as a first-line, non-invasive option for acute peroneal tendon tears. Full article

5q spinal muscular atrophy (5q-SMA) is a leading genetic cause of infant mortality. Presymptomatic intervention with disease-modifying therapies significantly improves motor outcomes, but effectiveness depends on early detection through newborn screening (NBS). Despite global 5q-SMA NBS expansion and recent Brazilian federal legislation, regional disparities and a lack of systematic monitoring hinder access to timely diagnosis and care. This study addresses these gaps by evaluating a statewide pilot program in São Paulo. We used multiplex real-time PCR to detect SMN1 exon 7 deletions in dried blood spots, confirming SMN1/2 copy numbers via MLPA in positive cases. Under real-world conditions, timeliness key performance indicators were evaluated to assess operational efficiency. 194,714 newborns were screened with 14 positive cases, yielding a prevalence of 1:13,908. First-tier results and treatment initiation occurred at a median of 10.8 and 28 days of life, respectively. Notably, 78.6% of patients had two SMN2 copies, of which approximately half were symptomatic by the first evaluation, highlighting the critical need for rapid screening to prevent irreversible motor decline. Screening achieved 100% specificity. This pilot demonstrates the feasibility of 5q-SMA NBS within the Brazilian public health system, providing essential evidence to overcome logistical and socioeconomic barriers and support nationwide expansion. Full article

Background/Objectives: Oxidative stress is a major cause of impaired oocyte quality and early embryo development, a challenge that still needs to be addressed in assisted reproduction. Mesenchymal stem cell secretomes have been investigated as cell-free therapeutics with antioxidant activity and relevant anti-apoptotic effects. This study aimed to evaluate the effects of human amniotic membrane-derived mesenchymal stem cell-conditioned saline (AMSC-CS) as an injectable formulation on oxidative stress–related markers in ovarian tissue and preimplantation developmental outcomes. Methods: AMSC-CS was administered intravenously to female mice in a dose-dependent manner. Safety assessments were conducted to evaluate systemic and target organ toxicity within the dosage range. In vitro fertilization (IVF) outcomes and oxidative status in ovaries, oocytes, and embryos were evaluated following treatment with low, medium, and high doses of AMSC-CS (1, 3, and 5 μL/g). Results: As an injectable formulation, the safety assessments did not reveal systemic or target organ toxicity of AMSC-CS within the dosage range. Medium-to-high doses of AMSC-CS improved the expression of folliculogenesis-related genes and decreased oxidative stress and apoptosis signaling in ovarian tissue. At the high dose, AMSC-CS promoted preimplantation embryo development to the blastocyst and hatched blastocyst stages, along with improved blastocyst quality and reduced oxidative stress in oocytes and blastocysts. Conclusions: These findings suggest that AMSC-CS at medium-to-high doses, as an injectable formulation with antioxidant activity, may be a promising adjunct for assisted reproductive technologies. Full article