Quality assurance (QA) in radiation therapy is a critical component of ensuring accurate and consistent patient treatments, but many tasks are time consuming and rely on human visual acuity, which limits their accuracy. We aimed to automate monthly mechanical QA tests, improve measurement accuracy and precision, and decrease inter-user variability using a computer vision-based quality assurance (CVQA) system. A custom marker board incorporating four ArUco markers was created along with a custom camera holder that mounted onto the gantry head. OpenCV was utilized to automate tests for couch translation, collimator and table angles, collimator and table walkout, optical distance indicator (ODI), and field size detection. A GUI was created to guide users through the tests, determine passing status of measurements based on MPPG8.b criteria, and display image captures to allow users to troubleshoot if needed. Reproducibility tests were taken across four days. The system was tested against manual measurements by graph paper or digital level for each test. Field sizes and ODI were read by 12 different physicists to determine human variability and comparisons for CVQA. The CVQA system took 5 min to set up and 7 min to perform all tests. All field sizes, collimator/table angles, collimator/table walkout, and table translations were reproducible within 0.5 mm and 0.5°. ODI measurements were reproducible within 1 mm. Table travel, ODI, and walkout measurements agreed with manual measurements within 0.5 mm and 0.4°, except for vertical table motions that agreed within 0.9 mm due to the lens focus being optimized for the 100 cm SSD plane. The standard deviation between physicists for almost all symmetric and asymmetric jaws was larger than the reproducibility of CVQA. CVQA has been utilized for five years and has demonstrated ability to identify mechanical machine issues. CVQA successfully automates mechanical QA tasks, providing an efficient and precise system. CVQA is open source and freely available for academic institutions. Its adoption can improve workflow efficiency and consistency in clinical environments.
Background: Odontogenic keratocysts are developmental cysts of the jaws that often remain asymptomatic until they reach considerable size and are most frequently located in the mandibular angle and ramus regions. Due to their high recurrence potential, the optimal treatment approach remains controversial. The aim of this study was to evaluate treatment modalities associated with lower recurrence rates in odontogenic keratocysts. Material and Methods: Patients diagnosed with odontogenic keratocyst between 2000 and 2024 at the Department of Oral and Maxillofacial Surgery, Gazi University, were retrospectively evaluated. Associations between gender, age, lesion localization, histological subtype, treatment modality, and recurrence were analyzed. Statistical analyses were performed using SPSS for Windows (version 27). Results: A total of 291 cases were included, with an overall recurrence rate of 16.2%. The highest recurrence rate was observed in patients treated with enucleation (19.2%), whereas a lower recurrence rate was found in cases treated with marsupialization (5%). No recurrence was observed in patients who underwent resection. A statistically significant association was found between treatment modality and recurrence (p = 0.014). Conclusions: Treatment selection for odontogenic keratocysts should be carefully planned. In the present study, marsupialization was associated with a lower recurrence rate than enucleation in selected cases. However, because of the retrospective design and non-randomized treatment allocation, these findings should be interpreted with caution and should not be considered evidence of a causal relationship. Long-term clinical and radiological follow-up remains essential because of the potential for late recurrence.
The design of robotic graspers that can safely interact with deformable, damage-prone materials such as fruits, vegetables, and biological tissues remains an ongoing challenge in robotics. Conventional robotic graspers made of mostly rigid materials have limited compliance and tactile sensing, reducing their applicability to contact-rich manipulation of soft objects. In contrast, humans and animals can interact with their environments safely and intelligently through their bodies' structural properties and nervous systems' computational capabilities. In this article, we present the design and control of a soft grasper inspired by the sea slug, Aplysia californica, and compare its performance with rigid graspers. The soft jaws and actuators allow the grasper to mimic Aplysia's force sensing capability and its ability to conform to complex food as it grasps. Combining Synthetic Nervous Systems (SNSs), an artificial neural network model inspired by computational neuroscience, and network architectures inspired by Aplysia's feeding control circuitry, we designed distributed and interpretable pick-and-place controllers for the soft grasper and its rigid counterparts. During grasping, these controllers either command a fixed closure radius (feedforward position control) or cap the contact force at a predefined level (force feedback control). We first validated our approach in simulation, demonstrating that the controllers can perform pick-and-place behavior that is robust to sensor noise. We then extended the validation to the physical platform to quantitatively compare how much deformation these graspers induced on soft objects. Fruits such as strawberries, tomatoes, and avocados showed little deformation after they were handled by the soft grasper, suggesting that this approach might have significant agricultural uses. The experimental data suggest the value of the bioinspired soft grasper for soft object manipulation.
This study aimed to evaluate the accuracy of robotic computer-assisted implant surgery in edentulous patients and to compare differences in accuracy between implants placed in the maxilla and mandible, as well as between anterior and posterior regions. Six patients who voluntarily underwent autonomous robotic computer-assisted implant surgery (R-CAIS) using the YaKebot system and met the eligibility criteria were included in this study. Preoperative planning data and postoperative CBCT images were imported into the robotic software system for registration to calculate deviations between the designed and actual implant positions. The primary outcomes included global deviations at the implant platform and apex, angular deviation, as well as horizontal and vertical deviations at the platform and the apex. Deviations were compared among implants placed at different anatomical locations, with p < 0.05 considered statistically significant. Six edentulous patients underwent R-CAIS with a total of 42 implants placed. The mean deviation at the implant platform was 0.519 ± 0.216 mm, while the mean apex deviation was 0.508 ± 0.224 mm. The mean angular deviation was 0.634 ± 0.402°, and the mean vertical deviation was 0.298 ± 0.248 mm. The results showed that global deviations at the apex, global angular deviations, and platform vertical deviations tended to be lower in the anterior region than in the posterior region. However, none of these differences reached statistical significance (all p-values > 0.05). Implants in the maxilla exhibited overall smaller deviations than those in the mandible. Notably, the buccolingual deviation at the apex was significantly lower in the maxilla than in the mandible (p = 0.021). No other significant differences were found between the two jaws (all p > 0.05). In terms of deviation direction, the implants tended to deviate toward the buccal and distal directions and were positioned slightly more superficially than designed. R-CAIS can achieve high accuracy in implant placement in edentulous patients, supporting its broader clinical application in complex implant rehabilitation.
Temporomandibular disorders (TMD) are commonly accompanied by adaptive or degenerative osseous alterations of the mandibular condyle, and parafunctional oral behaviors may contribute to abnormal joint loading. This retrospective cross-sectional study investigated the association between self-reported parafunctional activities and cone-beam computed tomography (CBCT)-defined condylar remodeling patterns in adults with TMD. Consecutive patients diagnosed according to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) between June 2023 and June 2024 were reviewed, and 102 individuals with complete clinical and imaging data were included. Parafunctional behaviors were assessed using a structured questionnaire adapted from the Oral Behaviors Checklist, focusing on unilateral chewing, tooth clenching, bruxism, and preference for hard foods. Bilateral CBCT images were reconstructed in multiplanar views, and osseous changes (including cortical blurring/vanishing, defects, flattening, sclerosis, osteophytes, and cystic degeneration) were recorded and localized by quadrant. Multivariable logistic regression was used to identify behavioral factors independently associated with specific radiographic phenotypes. Hard-food preference was independently associated with cortical blurring/vanishing and with changes involving the anterolateral and posterolateral condyle as well as the articular tubercle. Habitual unilateral chewing showed an inverse association with anteromedial condylar changes. Bruxism and clenching did not remain significant after adjustment. These findings suggest that specific parafunctional behaviors, particularly hard-food preference, are associated with distinct CBCT-detected condylar remodeling patterns in TMD and support behavioral assessment and counseling during clinical evaluation.
The structural integrity of teeth after endodontic retreatment depends on the amount of remaining dentin. Excessive instrumentation can weaken roots and predispose them to fracture. This study evaluated the fracture resistance of maxillary premolars following non-surgical retreatment (NS-ReT) with Retreaty and XP-endo Rise systems. Forty-eight maxillary first premolar roots were randomly assigned to 4 groups (n = 12); G1-NC (Negative control, non-instrumented), G2-PC (Positive control, instrumented, not obturated), G3-RETY (Retreaty), and G4-XPER (XP-endo Rise). G2, G3 and G4 groups were prepared using the iRace system. Groups G3 and G4 were obturated with gutta-percha and resin sealer. Gutta percha removal was performed using Retreaty (G3-RETY) and XP-endo Rise retreatment files (G4-XPER). All samples were subjected to fracture testing using a universal testing machine & the maximum fracture load (N) was recorded. Gutta percha removal times (Tf) and total time of retreatment were also measured. Statistical analysis was performed using a mixed-model analysis of variance (ANOVA) (α = 0.05). The fracture resistance of G1-NC (942.92 ± 24.73 N) had significantly higher values compared to all other groups. Fracture values for the G2-PC (829.62 ± 71.55 N) and the G3-RETY (818.29 ± 73.14 N) did not significantly differ from each other (p = 1.000), but both were significantly higher than the G4-XPER (489.37 ± 33.47 N). The total time of retreatment was significantly reduced when using the G3-RETY (3.89 ± 0.84 min) compared to the G4-XPER (13.30 ± 2.05 min), p < .001. Teeth retreated using the Retreaty instruments demonstrated superior fracture resistance compared to XP-endo Rise and their values were comparable to the positive control group. Moreover, Retreaty file system showed faster gutta-percha removal and canal preparation during retreatments.
To evaluate dental and skeletal factors influencing spontaneous space closure and axial angulation of the second molar (P2M) and second premolar (SP) five years after permanent first molar (P1M) extraction. This retrospective cohort study included 79 patients (mean age 9.5 ± 1.6 years) with unilateral P1M extraction. Panoramic radiographs were analyzed at T1 (pre-extraction) and T2 (5-year follow-up). P2M developmental stages (Demirjian), initial vertical positions, and baseline skeletal parameters (gonial angle, condylar inclination, and antegonial notch angle) were assessed on T1 panoramic radiographs. Angulation changes were compared between the extraction and the non-extraction control sides. Complete space-closure status did not differ significantly among Demirjian developmental stages (p > 0.05). In the maxilla, P2M angulation changes differed significantly among developmental timing groups (p = 0.018). In the mandible, SP showed significant distal tipping within all developmental groups (p < 0.05), whereas no significant SP angulation change was observed in the maxilla. A significant positive correlation was identified between baseline antegonial notch angle and complete space closure (p = 0.011). Compared with the contralateral non-extraction side, the extraction side showed significant angular differences for both P2M and SP. The P2M developmental stage alone appeared insufficient for explaining complete space closure following unilateral P1M extraction. Post-extraction angular changes differed according to jaw and tooth type, and baseline antegonial notch angle showed an exploratory association with complete space closure. These findings suggest that selected panoramic observations may provide supplementary information during case assessment, but should not be interpreted as standalone predictive criteria. In children requiring P1M extraction, P2M developmental stage should not be used as the sole criterion for estimating spontaneous space closure. Expected post-extraction tipping patterns and selected panoramic findings, particularly the antegonial notch angle, may provide supplementary information during case assessment.
Le Fort I osteotomy is widely performed in orthognathic surgery for maxillary repositioning and for the treatment of dentofacial deformities and obstructive sleep apnea (OSA). Postoperative relapse remains a concern, particularly after large maxillary advancements, highlighting the importance of rigid fixation. This study aimed to determine which fixation technique provides the greatest rigidity. In this in vitro study, the biomechanical rigidity of five commonly used fixation techniques for Le Fort I osteotomies was evaluated using 150 polyurethane specimens with advancements of 5 mm and 10 mm. The techniques included two L-plates (A), four L-plates of different thicknesses (B and C), two precontoured Le Fort I plates (D), and a hybrid configuration with two precontoured Le Fort I plates combined with two L-plates (E). Resistance to vertical displacement was measured at 1, 3, and 5 mm using a biomechanical testing machine. Fixation E consistently showed the highest resistance across both advancement distances and all displacement intervals, significantly outperforming fixations A, C, and D. Fixation B demonstrated resistance comparable to fixation E, whereas fixation C showed inferior performance despite a similar configuration. Fixations A and D showed the lowest resistance, particularly at 10 mm advancement. Overall, fixation E provided the greatest rigidity, while techniques relying on only two plates were biomechanically less effective. Further clinical studies are required to determine the clinical relevance of these findings.
Arch width (AW) affects space availability and shifts the anchorage balance in extraction cases. This study aimed to investigate whether AW differs between patients treated with clear aligners (CAs) and those treated with conventional fixed appliances (FAs) following the extraction of four first premolars. This retrospective study included 60 Class I patients who underwent extraction of four first premolars and were treated with either CAs (Invisalign, Align Technology) or FAs (MBT prescription, 0.022-inch slot). The CAs group consisted of 3 males and 27 females (mean age, 24.53 ± 4.58 years), and the FAs group included 4 males and 26 females (mean age, 22.60 ± 3.92 years). In the CAs group, patients were instructed to change the aligners every 10 days and to wear them for at least 22 h per day. Digital dental casts and lateral cephalometric radiographs were obtained at the beginning (T1) and completion (T2) of treatment. Maxillary and mandibular intercanine, interpremolar, and intermolar widths were measured. Paired t-tests were used for intragroup comparisons, and independent t-tests were used for intergroup comparisons. Statistical significance was set at P <.05. Maxillary and mandibular incisors in the CAs group exhibited significantly greater retroclination than those in the FAs group (P <.05). No significant intergroup differences in AW were identified before treatment (P >.05). However, post-treatment measurements demonstrated significantly greater AW in the CAs group at the cusp level of the maxillary and mandibular canines (P <.05). Both groups exhibited statistically significant reductions in maxillary and mandibular interpremolar widths (P <.05), with a more pronounced decrease in the FAs group (P <.05). In the CAs group, intermolar AW remained stable (P >.05), whereas the FAs group showed a significant post-treatment reduction (P <.05). Moreover, following treatment, the achieved AW exceeded the ClinCheck-predicted values at the gingival level of both maxillary and mandibular molars (P <.05). In extraction cases, patients treated with CAs demonstrated a larger AW and greater lingual inclination of the anterior teeth than those treated with FAs. The relatively wider dental arches observed in the CAs group may have implications for space management during treatment. Additionally, the combination of a larger AW and greater incisor retroclination could impose excessive mechanical demands on the flexible aligner trays. Therefore, careful case selection is essential when considering extraction-based treatment with CAs.
Buds are continuously renewed sensory organs in which development, adult maintenance, and repair share overlapping molecular circuitry. During embryogenesis, WNT/β-catenin signaling promotes taste placode formation and placodal Shh expression, while SHH refines papilla spacing and restricts neighboring papilla formation. SOX2 functions as a taste-competence and progenitor maintenance factor. In adults, LGR5/LGR6-RSPO-WNT signaling sustains progenitor activity, and gustatory neurons are an important source of RSPO2; available genetic evidence is consistent with a neuron-derived contribution to the LGR5/LGR6 niche, and AAV-Cre-mediated neuron-specific ablation of Rspo2 in the petrosal ganglion led to near-complete loss of circumvallate taste buds. HH signaling from epithelial and neuronal sources further supports SOX2-dependent progenitor homeostasis. Lineage allocation is governed by transcriptional programs that include POU2F3/SKN-1a for sweet, umami, and bitter type II taste receptor cells, and ASCL1 with posterior-field NKX2-2 for type III presynaptic/sour cells. After denervation or irradiation, regeneration depends primarily on LGR5+/KRT14+ progenitors and may be supplemented, in specific injury contexts, by plasticity of a subset of K8-lineage taste receptor cells that acquire KRT14/SOX2/PCNA progenitor-like features. Key unresolved questions include the direct chromatin targets of taste lineage regulators (which remain to be defined by ChIP-seq in native taste progenitors), the identity of the type I cell selector, the contribution of dedifferentiation across injury models, and the degree to which mouse-derived networks are conserved in human taste biology.
To radiographically and histologically evaluate bone formation following alveolar ridge preservation (ARP) using octacalcium phosphate collagen composite (OCP/Col). A total of 42 patients (48 sites) completed the study. The primary comparison was performed between an OCP/Col-treated molar group (OCP-M) and an atelocollagen-treated molar control group (Control-M). In addition, an OCP/Col-treated incisor-premolar group (OCP-IP) was included as an exploratory subgroup to assess tooth-type effects. Alveolar bone dimensional changes were assessed using cone-beam computed tomography (CBCT) immediately after ARP and at 6 months. Guided hard tissue biopsies were performed to quantify the proportions of mature bone and residual granules. Changes in buccal bone height were + 0.7 mm (± 2.2) in the OCP-M group, - 0.6 mm (± 0.7) in the Control-M group, and + 3.7 mm (± 3.9) in the OCP-IP group. The difference between the OCP-M and Control-M groups was significant (p = 0.041), as was that between the OCP-IP and OCP-M groups (p = 0.038). Histologically, the proportion of mature bone in the alveolar crest region was significantly higher in the OCP-M group (38.14% ± 20.96) than in the Control-M group (18.28% ± 16.52, p = 0.009). Within the limitations of this study, ARP using OCP/Col resulted in increased buccal bone height and enhanced bone maturation at the alveolar crest compared with atelocollagen alone. OCP/Col may serve as a stand-alone graft material for ARP and may facilitate minimally invasive, prosthetically driven implant therapy. UMIN000059637 (UMIN Clinical Trials Registry).
Reports on the association between hemophilia and pediatric diabetes are very scarce in the literature, with no more than four worldwide. This report describes the case of a 14-year-old male with severe hemophilia A and type 1 diabetes who was brought to the emergency department due to fever and bruising on his back and jaw following trauma. The patient responded well to plasma-derived factor VIII, drainage, antibiotic therapy, and management with NPH and Regular insulin. There were no problems with the use of subcutaneous insulins during hospitalization. Previously reported cases in the literature describe potential bleeding and bruising associated with devices used for managing pediatric diabetes. However, severe bleeding and bruising that significantly impede diabetes treatment do not appear to be present, although individualized management is still required.
Background/Objectives: Contemporary patient-specific subperiosteal implants have re-emerged as graftless solutions for oral and maxillofacial rehabilitation, driven by advances in digital planning, CAD/CAM workflows, additive manufacturing, and biomaterial engineering. Their indications have progressively expanded from severely atrophic edentulous jaws to segmental defects, single-tooth replacement, congenital craniofacial anomalies, salvage situations, and oncologic reconstruction. This scoping review aimed to map the current evidence on modern patient-specific subperiosteal implants, focusing on indications, workflow, design principles, materials, outcomes, complications, and maintenance. Methods: A scoping review was conducted according to PRISMA-ScR principles to identify clinical studies, case series, case reports, systematic and scoping reviews, technical notes, finite element analyses, in vitro studies, and relevant translational investigations dealing with contemporary custom-made or CAD/CAM subperiosteal implants. The evidence was narratively synthesized according to clinical indication and thematic domains, including full-arch rehabilitation, sectional and single-tooth applications, congenital and post-oncologic defects, rescue indications, biomechanics, material selection, surface response, prosthetic protocols, and complication management. No quantitative meta-analysis was performed because of the scoping design and the substantial heterogeneity of study types, indications, implant systems, outcome definitions, and follow-up durations. Results: The final evidence map included 116 records, of which 56 were unique human clinical records with extractable denominators and 60 were biomechanical, in vitro, surface-biology, review, consensus, historical, or conceptual records. Of the 56 unique clinical records, 49 were mapped within the six indication-level clinical sections, while seven were retained as cross-cutting clinical evidence addressing patient-reported outcomes, design-related complications, bone apposition, anchorage strategy, comparative graftless rehabilitation, or reconstructive/prosthetic principles. The six indication-level sections included 52 clinical-record assignments: 15 for full-arch rehabilitation, 13 for segmental or sectional rehabilitation, one for single-tooth rehabilitation, four for congenital or craniofacial indications, 13 for post-oncologic or post-ablative reconstruction, and six for rescue or salvage indications. Because three records addressed more than one indication, these counts represent indication-level assignments rather than mutually exclusive clinical records. Reported survival in most short- to mid-term clinical series was generally high, commonly ranging from 90% to 100%, although lower values of 70-80% were reported in selected longer-term cohorts and survival clearly overestimated clinical success in some studies. Expanding applications include posterior mandibular and maxillary defects, lateral incisor agenesis, cleft-related or syndromic deformities, maxillectomy reconstruction, obturator support, and hybrid rehabilitation with endosseous implants; however, evidence for the indications at the extremes of this spectrum-single-tooth replacement and primary oncologic reconstruction-remains limited to small, largely single-group case series and reports. Soft-tissue events, including dehiscence, mucositis, recession, and framework exposure, were the dominant complications and showed wide variability, with reported recession/exposure rates ranging from approximately 10% in some sectional and full-arch series to as high as 65% in bilateral maxillary cohorts; their clinical significance varied from asymptomatic stable findings to progressive inflammatory complications requiring revision. Conclusions: Patient-specific subperiosteal implants represent a promising and increasingly versatile reconstructive option; however, the present findings should be interpreted as evidence mapping rather than as definitive comparative evidence. Their clinical use should remain highly selective, prosthetically driven, and supported by meticulous planning, rigid fixation, soft-tissue management, and structured maintenance. Standardized success criteria, longer follow-up, and comparative prospective studies are required.
Factors associated with sleep bruxism (SB) in children with mixed dentition remain incompletely understood. This study examined the relationship between sleep bruxism and sleep behaviors, oral habits, temporomandibular disorders (TMD), and health status in Turkish schoolchildren during the mixed dentition stage. In this cross-sectional study, a representative sample of 452 schoolchildren was assessed. Sleep bruxism was assessed by a subjective-based assessment (parental report of tooth grinding during sleep). During the clinical oral examination, tooth wear, free-way space, maximum mouth opening, and signs of TMD were recorded. Parents or caregivers completed a questionnaire on sociodemographic factors, general health, sleep behavior, oral habits, and recent life changes. Associations were analyzed using the χ² or Fisher's exact test, the Mann-Whitney U test, and logistic regression, with effect sizes (Cramér's V, odds ratios, and r). Sleep bruxism was identified in 22.6% of the 452 children, with no significant difference between genders (p = .077). Regarding health status, SB was more common among children with allergic rhinitis (p < .001; OR = 2.42, 95% CI 1.50-3.91). Regarding TMJ/jaw function and oral habits, SB was associated with head/jaw trauma, difficulty opening the mouth, TMJ pain, pain while chewing hard foods, biting hard foreign objects, chewing hard candies or ice, and leaning the jaw against the hand (all p < .05). Regarding sleep-related variables, SB was associated with snoring, drooling on the pillow, bedwetting, restless sleep, and mouth-breathing (all p < .05). Regarding family factors, SB was associated with parental and sibling grinding and with parental divorce (all p < .05). TMD symptoms were present in 22.5% of bruxism-positive children compared with 12.3% of bruxism-negative children (p = .010; OR = 2.08, 95% CI 1.18-3.65); all effect sizes were small (Cramér's V ≤ 0.21). No significant association was found between SB and tooth wear (p = .282). In multivariable analysis, allergic rhinitis, parental history of grinding, drooling on the pillow, restless sleep, and TMD remained independently associated with SB. Sleep bruxism was associated with several sleep-related, respiratory, behavioral, and family-history factors and with TMD signs and symptoms, although all associations were of small magnitude. After multivariable adjustment, allergic rhinitis, parental history of grinding, drooling on the pillow, restless sleep, and TMD were independently associated with SB. Given the cross-sectional design, these findings indicate associations rather than causal or aetiological relationships. Approved by the Ethics Committee of Dokuz Eylul University (2024/13-18).
The diagnosis of primary bone tumours of the jaw often presents as a diagnostic dilemma. Overlap in clinical, radiological, and histological features between benign lesions like juvenile trabecular ossifying fibroma (JTOF); osteoblastoma (OB) and malignant tumours like low-grade osteosarcoma (LGOS) makes the diagnosis challenging. While osteosarcoma is a malignant tumour with poor prognosis requiring aggressive treatment, benign lesions have generally favourable outcome. This study aimed to assess the immunohistochemical expression of murine double minute 2 (MDM2) and Cyclin-dependent kinase 4 (CDK4) in low-grade osteosarcoma and benign osseous lesions. Immunohistochemical analysis was performed on tissue samples from diagnosed cases of LGOS, JTOF, and OB. The expression levels of MDM2 and CDK4 were analysed and compared across the three groups. We found significantly higher expression of MDM2 and CDK4 in low-grade osteosarcoma compared to JTOF which showed negative expression in all of the cases. Osteoblastoma showed inconsistent and focal positivity contrary to OS where strong and diffuse expression of both the markers was observed. A strong co-expression of both the markers was also noted in 94% of OS cases. Immunohistochemistry for MDM2 and CDK4 is a valuable diagnostic tool in differentiating low-grade osteosarcoma from benign mimics. This approach provides a cost-effective, reliable, and accurate means for diagnosing jaw bone tumours, particularly when tissue samples are insufficient or on small incisional biopsies where accurate diagnosis is of prime importance.
In pediatric patients, tooth extraction frequently results in unpleasant postoperative complications, including pain, inflammation, and bleeding. These painful experiences contribute to a child's anxiety, which may reduce his compliance with subsequent dental treatments. This study aimed to evaluate the efficacy of photobiomodulation therapy (PBMT) as an adjunctive treatment to enhance wound healing and manage post-extraction pain in children. This was a double-blind, split-mouth, randomized controlled clinical trial. A total of 18 children with a mean age of 6.5 years were included; each child had one primary molar bilaterally indicated for extraction. Eligible sides were randomly assigned to either the test group (n = 18) receiving PBMT using a diode laser of wavelength 660 nm, an output power of 100 mW, and an application duration of 60 s (total energy of 6 J), or to the control group (n = 18) (placebo treatment). A one-week interval was implemented between the extraction of the first and contralateral side as a washout period to optimize post-operative comfort and function. Both groups received post-extraction instructions. Primary outcomes included wound healing, assessed by Landry, Turnbull, and Howley wound healing index, and post-extraction pain, monitored over one week using a self-reported questionnaire assessing pain, discomfort, analgesic consumption, daily activities, and jaw-function impairment. Data were analyzed using the Wilcoxon signed-ranks test, and McNemar test, with significance defined as p < 0.05. At day 7, the test group demonstrated significantly superior wound healing scores (Median: 5.00) compared to the placebo group (Median: 4.00) (P = 0.002*). Furthermore, PBMT significantly reduced the subjective feeling of discomfort on the first evening (P = 0.02*). Over the one-week follow-up, the test group showed no analgesic consumption compared to 33.3% in the placebo group (P = 0.03*). It also reported significantly less difficulty with chewing on the extraction site, chewing soft food, and difficulty with taking a big bite compared to the placebo group; with percentages (38.9% vs.88.9%, P = 0.004*), (0% vs.33.3%, P = 0.03*), and (33.3% vs.72.2%, P = 0.04*), respectively. Photobiomodulation therapy is an effective adjunctive treatment following primary mandibular molar extraction. It significantly accelerates wound healing, reduces discomfort, and improves functional recovery by significantly reducing the need for post-operative analgesics. This study was prospectively registered on March 6, 2025 (Trial registration number: NCT07033403 ).
The fundamental cause of osteoporosis lies in the imbalance of bone remodeling triggered by the overactivation of osteoclasts. Although existing anti-resorptive medications demonstrate definitive therapeutic efficacy, their lack of lesion specificity often leads to off-target systemic exposure. This, in turn, frequently results in clinical side effects-such as excessive suppression of bone turnover and osteonecrosis of the jaw-which severely compromise the safety and patient compliance of long-term treatment. Consequently, there is an urgent clinical demand for precision delivery strategies with lesion-specific targeting. During the process of bone resorption, osteoclasts actively secrete protons into the sealed zone via proton pumps, establishing a localized, extreme acidic microenvironment. This biological phenomenon provides a natural physicochemical "switch" for achieving site-specific drug delivery. Based on these considerations, this paper introduces the "differential effective site exposure" strategy. This approach aims to leverage the acidic gradient to drive the spatial sequestration and active responsiveness of nanocarriers, thereby maximizing the effective drug exposure gain at bone resorption sites relative to non-target tissues. We systematically review the design principles and drug release kinetic profiles of three categories of acid-responsive nanocarriers based on chemical bond cleavage, charge reversal, and inorganic matrix degradation. Furthermore, this study highlights how biomimetic materials, represented by amorphous calcium carbonate, restore the balance of bone remodeling through a synergistic mechanism of neutralizing the pathological acidic environment and releasing osteogenic active ions. Finally, the paper evaluates the challenges posed by disease heterogeneity and discusses the translational bottlenecks in industrial-scale production and long-term biosafety. This work is intended to provide a theoretical framework and design rationale for the development of highly selective and safe next-generation precision anti-osteoporotic therapeutics.
Everolimus is approved for the treatment of advanced renal cell carcinoma after VEGF-targeted therapy, metastatic HR-positive/HER2-negative breast cancer in combination with exemestane, and other oncologic indications. However, an intravenous option has not been developed, largely due to its pronounced hydrophobicity and limited oral bioavailability of approximately 15-20%. In this study, we report the development of Sapu003, a novel intravenous Everolimus formulation enabled through the Deciparticle™ platform. A diverse library of mPEG-based block copolymers was evaluated for their ability to encapsulate Everolimus and self-assemble into stable nanoparticle structures. mPEG-Chol was ultimately selected based on its favorable biocompatibility characteristics. In addition to Everolimus, mPEG-Chol and related analogs demonstrated broad formulation compatibility with multiple hydrophobic therapeutics, including Sirolimus, Tacrolimus, Cyclosporine, as well as representative peptides and polyketides. Clinical manufacturing was conducted in a cGMP environment over a 7-day production cycle. Production was carried out under amber light using light-protective vials to reduce drug degradation. The bulk material was sterile-filtered, and subsequent fill/finish/lyophilization operations were performed under temperature-controlled conditions with high precision in fill accuracy (≥98%). After reconstitution, the final product yielding uniform Deciparticles™ that met predefined sterility and particle size criteria. Stability studies demonstrated that the formulation remained stable for at least one month at 5 °C and retained acceptable in-use stability for at least 24 h at room temperature. The process was successfully scaled beyond 10 g, supporting an ongoing Phase 1b open-label dose escalation clinical study of Sapu003 in combination with exemestane in patients with advanced mTOR-sensitive solid tumors (NCT07369505). In vivo evaluation demonstrated strong antitumor efficacy following intravenous administration (QW × 3), with tumor growth inhibition reaching 97-98% in the U-87MG glioblastoma xenograft model. No evidence of phlebitis was observed with repeated tail vein dosing. In this model, Sapu003 dosed weekly showed superior tumor suppression compared with oral Everolimus. Collectively, screening of a mPEG-block copolymer library identified mPEG-Chol as a lead excipient capable of consistently forming stable Deciparticles™ with sub-20 nm mean particle size. The resulting intravenous Everolimus formulation demonstrated scalable manufacturing, favorable stability, and potent antitumor activity in preclinical models, supporting further clinical evaluation of Sapu003 in advanced solid tumors.
The maxillary canal system in Cynognathus and Diademodon is described. The hypothesis that expansion of the maxillary sinus represents a synapomorphy of the clade Cynognathia is supported. A trend towards the reduction of the inferior palpebral ramus is proposed.
Parrots (Order: Psittaciformes) are renowned for their high bite force (BF) and morphological correlates thereof, including a highly mobile skull and two unique mandibular adductor muscles-m. pseudomasseter and m. ethmomandibularis, with the former being hypothesized to increase force output. High BF has been hypothesized to relate to their generally high seed and grain consumption. However, both in vivo and anatomical BF estimates for this group are limited, and the few empirical studies that exist found no relation between BF and diet in these birds. BF can be anatomically estimated via analysis of the physiological cross-sectional area (PCSA) of each masticatory muscle combined with biomechanical modeling of the skull. Simple single-joint models, based on mammalian mechanics, may not be adequate for application to the complex parrot skull. To this end, we performed sharp dissection and then used chemical digestion in nitric acid to collect masticatory muscle fiber data across a broad sample of 27 species. We then analyzed three biomechanical models of BF estimation as well as possible dietary correlates of the resulting estimates. Our results confirm that parrots do indeed have high BF abilities (up to 242 N in the largest species) and that muscle mass, PCSA, and BF scaled positively against body mass. As previously observed, dietary mechanical properties showed no significant correlation to BF. The two biomechanical models that reflect the more elaborate jaw movements possible in birds estimated greater BF than the simpler mammalian-like model and should be validated with future in vivo BF experiments.