Elucidating the role of FOS in modulating the immune microenvironment through fibroblast and myeloid cell regulation in locoregional recurrent HNSCC.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) presents a significant clinical challenge, particularly due to its high propensity for locoregional recurrence. Current research underscores the need to unravel the complex interactions within the tumor microenvironment. This study addresses the critical gap in understanding how FOS modulates the immune landscape in HNSCC, with a focus on its influence on fibroblast and myeloid cell dynamics. METHODS: Employing a comprehensive approach, we analyzed tissue samples from HNSCC patients and adjacent non-cancerous tissues using bulk RNA sequencing complemented by in-depth bioinformatics analyses, including gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, and immune infiltration assessment. A pivotal aspect of our research involved dissecting single-cell RNA-seq data from GSE234933 to elucidate the cell-type-specific expression of FOS. RESULTS: We found that FOS expression varies significantly in different cell populations in the HNSCC tumor microenvironment, especially in fibroblasts and myeloid cells. This expression difference may reflect the different roles of these cells in tumor progression and their impact on the tumor microenvironment. CONCLUSION: Our results uncover a significant correlation between FOS expression and key immune and hypoxia-related pathways, suggesting its integral role in the tumor microenvironment. These findings not only enhance our understanding of HNSCC pathogenesis but also highlight FOS as a potential therapeutic target. This study marks a significant step towards addressing the urgent need for targeted interventions in HNSCC, particularly in the context of locoregional recurrence.

Automatic virtual reconstruction of maxillofacial bone defects assisted by ICP (iterative closest point) algorithm and normal people database.

OBJECTIVES: The aim of this study was to propose and validate an automatic approach based on iterative closest point algorithm for virtual complement and reconstruction for maxillofacial bone defects. MATERIALS AND METHODS: A 3D craniomaxillofacial database of normal Chinese people including 500 skull models was established. Modified iterative closest point (ICP) algorithm was developed to complete bone defects automatically. The performances were evaluated by two approaches: (1) model experiment, virtual bony defects were created on 30 intact normal skull models not included in the database. For each defect model, the algorithm was applied to select the reference skull model from the database. 3-Dimensional and 2-dimensional comparison were conducted to evaluate the error between reference skull model with original intact model. Root mean square error (RMSE) and processing time were calculated. (2) Clinical application, the algorithm was utilized to assist reconstruction of 5 patients with maxillofacial bone defects. The symmetry of post-operative skull model was evaluated by comparing with its mirrored model. RESULTS: The algorithm was tested on an CPU with 1.80 GHz and average processing time was 493.5 s. (1) Model experiment, the average root-mean-square deviation of defect area was less than 2 mm. (2) Clinical application, the RMSE of post-operative skull and its mirrored model was 1.72 mm. CONCLUSION: It is feasible using iterative closest point algorithm based on normal people database to automatically predict the reference data of missing maxillofacial bone. CLINICAL RELEVANCE: An automated approach based on ICP algorithm and normal people database for maxillofacial bone defect reconstruction has been proposed and validated.

High-performance autostereoscopic display based on the lenticular tracking method.

We propose a novel full-parallax autostereoscopic display based on a lenticular tracking method to achieve separation between the viewing angle and image resolution and to improve these two parameters simultaneously. The proposed method enables the viewing angle to be independent of the image resolution and has the potential to solve the long-term trade-off problem in integral photography. By employing the lenticular lens array instead of the micro-lens array in integral photography with viewing tracking, the proposed method shows a high-image resolution and wide viewing angle 3D display with full parallax. A real-time tracking and rendering algorithm for the display method is also proposed in this study. The experimental results, compared with those of the conventional integral photography display and the tracking-based integral photography display, demonstrate the feasibility of this lenticular tracking display technology and its advantages in display resolution and viewing angle, suggesting its potential in practical three-dimensional applications.

One-shot neuroanatomy segmentation through online data augmentation and confidence aware pseudo label.

Recently, deep learning-based brain segmentation methods have achieved great success. However, most approaches focus on supervised segmentation, which requires many high-quality labeled images. In this paper, we pay attention to one-shot segmentation, aiming to learn from one labeled image and a few unlabeled images. We propose an end-to-end unified network that joints deformation modeling and segmentation tasks. Our network consists of a shared encoder, a deformation modeling head, and a segmentation head. In the training phase, the atlas and unlabeled images are input to the encoder to get multi-scale features. The features are then fed to the multi-scale deformation modeling module to estimate the atlas-to-image deformation field. The deformation modeling module implements the estimation at the feature level in a coarse-to-fine manner. Then, we employ the field to generate the augmented image pair through online data augmentation. We do not apply any appearance transformations cause the shared encoder could capture appearance variations. Finally, we adopt supervised segmentation loss for the augmented image. Considering that the unlabeled images still contain rich information, we introduce confidence aware pseudo label for them to further boost the segmentation performance. We validate our network on three benchmark datasets. Experimental results demonstrate that our network significantly outperforms other deep single-atlas-based and traditional multi-atlas-based segmentation methods. Notably, the second dataset is collected from multi-center, and our network still achieves promising segmentation performance on both the seen and unseen test sets, revealing its robustness. The source code will be available at https://github.com/zhangliutong/brainseg.

Single-cell integrated transcriptomics reveals the role of keratinocytes in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a prevalent malignant tumor with significant morbidity and mortality. Understanding the molecular mechanisms of HNSCC and identifying prognostic markers and therapeutic targets are crucial for improving patient outcomes. In this study, we utilized single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data to comprehensively analyze HNSCC at the cellular level. We identified keratinocytes as the predominant cell type in tumor samples, suggesting their potential role in HNSCC development. Through hdWGCNA co-expression network analysis, we identified gene modules associated with HNSCC progression. Furthermore, we constructed a prognostic model based on specific genes and demonstrated its robust predictive performance in multiple datasets. The model exhibited strong correlations with immune cell infiltration patterns and signaling pathways related to tumor progression. Additionally, drug sensitivity analysis revealed potential chemotherapeutic targets for HNSCC treatment. Our findings provide valuable insights into the molecular characteristics and immune microenvironment of HNSCC, offering new perspectives for prognosis prediction and therapeutic interventions in clinical practice. Further research is warranted to validate and expand upon these findings, ultimately improving patient outcomes in HNSCC.

PPARG and the PTEN-PI3K/AKT Signaling Axis May Cofunction in Promoting Chemosensitivity in Hypopharyngeal Squamous Cell Carcinoma.

It has been demonstrated that PPARG may interact with the PTEN-PI3K/AKT pathway, contributing to its involvement in the chemotherapy treatment of hypopharyngeal squamous cell carcinoma (HSCC). However, the underlying mechanism remains largely unknown. In this study, gene expression profiles of 17 HSCC patients, comprising 8 chemotherapy-sensitive patients (CSP) and 9 chemotherapy-nonsensitive patients (CNSP), were collected and analyzed to investigate expression patterns, correlations, influencing factors of the PPARG-PTEN-PI3K/AKT pathway, and its role in regulating chemosensitivity. The results revealed significantly increased expression (p < 0.04) of AKT1, AKT2, AKT3, PIK3CA, PPARG, and PTEN in the CSP group compared to the CNSP group. Specifically, AKT2 exhibited significant overexpression in tumor tissue (p = 0.01), while AKT2, AKT3, PPARG, and PTEN displayed significant increases in normal tissue (p ≤ 0.04). Positive correlations (R ∈ [0.43, 0.71], p < 0.014) were observed between PIK3CA, AKT1, AKT2, AKT3, and PTEN, with AKT2, AKT3, and PTEN also showing significant correlations with PPARG (R ∈ [0.35, 0.47], p < 0.04). Age, gender, and disease stage had no influence on PPARG, PIK3CA, and PTEN expression, but they may affect AKT expressions. Pathway analysis revealed that PPARG may interact with the PTEN-PI3K/AKT signaling pathway, playing a crucial role in regulating chemosensitivity in the normal tissue microenvironment. Our results suggest that AKT1 and PIK3CA may be associated with chemosensitivity in HSCC tumor cells, while PPARG and PTEN might exhibit a correlation with a specific segment of the PI3K/AKT pathway, potentially influencing chemosensitivity in the normal tissue microenvironment of HSCC patients.

Genetic predisposition to milder forms of COVID-19 may provide some resilience to head and neck cancers.

Introduction: The impact of the COVID-19 pandemic on head and neck cancer (HNC) has been suggested, but the causal relationship remains unclear. Methods: We explore this connection by utilizing the Mendelian randomization (MR) approach applied to publicly available genome-wide association study (GWAS) summary datasets for COVID-19 and HNC. The datasets included critical COVID-19 (13,769 cases, 1,072,442 controls), hospitalized COVID-19 (32,519 cases, 2,062,805 controls), SARS-CoV-2 infection (122,616 cases, 2,475,240 controls), and HNC (2,131 cases, 287,137 controls). Mechanistic underpinnings of the causal relationships identified by MR analysis were explored through functional annotation augmented by AI-based literature data mining. Results: Surprisingly, a genetic predisposition to contracting a milder form of COVID-19 substantially reduced the risks of developing HNC (OR: 0.52, 95% CI: 0.35-0.78, p = 1.42E-03), with no significant association between genetic liability to severe COVID-19 and the risk of HNC detected. Additionally, our findings highlighted 14 genes linked to SARS-CoV-2 infection, potentially playing a protective role in the context of HNC. These genes include OAS1, LOC107985887, BCL11A, DPP9, LOC107984685, LINC02326, MUC4, NXPE3, IFNAR2, LZTFL1, LOC105372437, NAPSA, LOC105376622, LOC107986082, and SLC6A20. Conclusion: Our study emphasizes the protective role of the genetic liability to milder COVID-19 in reducing the risk of HNC while refuting a causal relationship between severe COVID-19 and HNC.

Exploring the Anticancer Properties of Sakuranin Flavanone in Human Oropharyngeal Squamous Carcinoma Cells by Studying Its Effects on Caspase-driven Apoptosis, Mitochondrial Membrane Potential (MMP) Loss, Cell Migratory and Invasiveness and m-TOR/PI3K/AKT Signalling Pathway.

Sakuranin is a flavanone which is a class of flavonoids found abundantly in Prunus species. Flavonoids have been long known for their anticancer properties against a range of human cancers. However, there are no previous reports on the anticancer effects of sakuranin flavanone molecule. This study was designed to study the anticancer effects of sakuranin against human oropharyngeal carcinoma cells along with investigating its effects on caspase-mediated apoptosis, mitochondrial membrane potential (MMP) loss, cell migration and invasion and m-TOR/PI3K/AKT signalling pathway. MTT assay was used to study effects on cell viability. The apoptotic studies were carried out through AO/EB staining, annexin V/FITC staining, comet assay and western blotting assay. Transwell chambers assay was used to study effects on cell migration and invasion. Flow cytometry was used to study effects of Sakuranin on mitochondrial membrane potential loss (MMP). Finally, western blotting was used to investigate m-TOR/PI3K/AKT signalling pathway. Results indicated that Sakuranin led to potent cell proliferation inhibition in a dose-dependent manner. Sakuranin also induced apoptotic cell death as indicated by fluorescence microscopy and annexin V/FITC staining assays. The apoptotic induction was mediated via activation of caspase-3, caspase-9, and Bax while as it led to downregulation of Bcl-2. Sakuranin also caused inhibition of cell migration and cell invasion along with causing significant decrease in MMP. Sakuranin also caused inhibition of expressions of proteins related with m-TOR/PI3K/AKT signalling pathway. In conclusion, the current findings clearly indicate anticancer effects of Sakuranin flavanone in human oropharyngeal cancer cells and are mediated via caspase activated apoptosis, inhibition of cell migration and invasion, loss of mitochondrial membrane potential and targeting m-TOR/PI3K/AKT signalling pathway.

A Comparative Evaluation of Optical See-through Augmented Reality in Surgical Guidance.

During traditional surgeries, planning and instrument guidance is displayed on an external screen. Recent developments of augmented reality (AR) techniques can overcome obstacles including hand-eye discoordination and heavy mental load. Among these AR technologies, optical see-through (OST) schemes with stereoscopic displays can provide depth perception and retain the physical scene for safety considerations. However, limitations still exist in certain AR systems and the influence of these factors on surgical performance is yet to explore. To this end, experiments of multi-scale surgical tasks were carried out to compare head-mounted display (HMD) AR and autostereoscopic image overlay (AIO) AR, concerning objective performance and subjective evaluation. To solely analyze effects brought by display techniques, the tracking system in each included display system was identical and similar tracking accuracy was proved by a preliminary experiment. Focus and context rendering was utilized to enhance in-situ visualization for surgical guidance. Latency values of all display systems were assessed and a delay experiment proved the latency differences had no significant impact on user performance. Results of multi-scale surgical tasks showed that HMD outperformed in detailed operations probably due to stable resolution along the depth axis, while AIO had better performance in larger-scale operations for better depth perception. This paper helps point out the critical limitations of current OST AR techniques and potentially promotes the progress of AR applications in surgical guidance.

Role of PPARG in Chemosensitivity-Regulating Network for Hypopharyngeal Squamous Cell Carcinoma.

PPARG has been reported to promote chemosensitivity in hypopharyngeal squamous cell carcinoma (HSCC). However, few studies tested its significance in the texture of a complex molecular network regulating chemosensitivity in HSCC. Here, we first employed RNA expression data analysis and literature data mining to uncover candidate genes related to HSCC chemosensitivity. Then, we constructed the molecular network regulating chemosensitivity in HSCC. After that, we employed degree centrality (DC) and weighted centrality (WC) to test the significance of PPARG within the regulating network. Pathway enrichment was done to study the cofunctions of PPARG and the rest of the genes within the network. The findings of our study contribute to the construction of a comprehensive network that regulates HSCC chemosensitivity, consisting of 57 genes, including PPARG. Notably, within this network, PPARG demonstrates a ranking of #5 and #13 based on DC and WC, respectively. Moreover, PPARG is connected to 29 out of the 57 genes and plays roles in multiple functional groups. These top related genes include AKT1, TP53, PTEN, MAPK1, NOTCH1, BECN1, PTGS2, SPP1, and RAC1. PPARG gets enriched in several key functional groups that have been implicated in the regulation of chemosensitivity, including those associated with the response to nutrients, vitamins, and peptides, the cellular response to chemical stress, and the regulation of hormone secretion and growth. Our results emphasize the involvement of PPARG and its interconnectedness with other genes in the regulation of HSCC chemosensitivity.

An accurate 3D augmented reality navigation system with enhanced autostereoscopic display for oral and maxillofacial surgery.

BACKGROUND: Oral and maxillofacial surgery demands high precision navigation to achieve optimal surgical outcomes. Augmented reality (AR) has been a promising solution for intuitive and accurate guidance, whereas existing systems have room for improvement. METHODS: We propose a high quality and accurate in situ AR navigation system. Enhanced image quality is achieved by deploying eye tracking in lenticular-based autostereoscopic display. Viewpoint tracking and optical tracking are integrated to assure accurate in situ images. RESULTS: The proposed system can provide in situ AR images in real-time, with a viewing angle of 59.5° × 49.1°, 3D image resolution of 0.35 × 0.21 mm, and image accuracy of 0.99 ± 0.70 mm. A maxillary drilling experiment obtains average position error of 1.12 ± 0.30 mm and localization time of 8.7 ± 3.9 s, significantly better than conventional 2D navigation system. CONCLUSIONS: The proposed system can display high-quality AR images and therefore reduce positioning error and operating time.

Augmented reality navigation with ultrasound-assisted point cloud registration for percutaneous ablation of liver tumors.

PURPOSE: We present a novel augmented reality (AR) surgical navigation method with ultrasound-assisted point cloud registration for percutaneous ablation of liver tumors. A preliminary study is carried out to verify its feasibility. METHODS: Two three-dimensional (3D) point clouds of the liver surface are derived from the preoperative images and intraoperative tracked US images, respectively. To compensate for the soft tissue deformation, the point cloud registration between the preoperative images and the liver is performed using the non-rigid iterative closest point (ICP) algorithm. A 3D AR device based on integral videography technology is designed to accurately display naked-eye 3D images for surgical navigation. Based on the above registration, naked-eye 3D images of the liver surface, planning path, entry points, and tumor can be overlaid in situ through our 3D AR device. Finally, the AR-guided targeting accuracy is evaluated through entry point positioning. RESULTS: Experiments on both the liver phantom and in vitro pork liver were conducted. Several entry points on the liver surface were used to evaluate the targeting accuracy. The preliminary validation on the liver phantom showed average entry-point errors (EPEs) of 2.34 ± 0.45 mm, 2.25 ± 0.72 mm, 2.71 ± 0.82 mm, and 2.50 ± 1.11 mm at distinct US point cloud coverage rates of 100%, 75%, 50%, and 25%, respectively. The average EPEs of the deformed pork liver were 4.49 ± 1.88 mm and 5.02 ± 2.03 mm at the coverage rates of 100% and 75%, and the average covered-entry-point errors (CEPEs) were 4.96 ± 2.05 mm and 2.97 ± 1.37 mm at 50% and 25%, respectively. CONCLUSION: Experimental outcomes demonstrate that the proposed AR navigation method based on US-assisted point cloud registration has achieved an acceptable targeting accuracy on the liver surface even in the case of liver deformation.

Statistical and individual characteristics-based reconstruction for craniomaxillofacial surgery.

PURPOSE: In craniomaxillofacial (CMF) surgery planning, a preoperative reconstruction of the CMF reference model is crucial for surgical restoration, especially the reconstruction of bilateral defects. Current reconstruction algorithms mainly generate reference models from the image analysis aspect, however, clinical indicators of the CMF reference model mostly consider the distribution of anatomical landmarks. Generating a reference model with optimal clinical evaluation helps promote the feasibility of an algorithm. METHODS: We first build a dataset with 100 normal skull models and then calculate a statistical shape model (SSM) and the distribution of normal cephalometric values, which indicate the statistical features of a population. To further generate personalized reference models, we apply non-rigid registration to align the SSM with the defect skull model. An evaluation standard to select the optimal reference model considers both global performance and anatomical evaluation. Moreover, we develop a landmark detection network to improve the automatic level of the algorithm. RESULTS: The proposed method performs better than methods including Iterative Closest Point and SSM. From a global evaluation aspect, the results show that the RMSE between the reference model and the ground truth is [Formula: see text] mm, the percentage of vertices with error below 2 mm is [Formula: see text]% and the average faces distance is [Formula: see text] mm (better than the state-of-the-art method). From the anatomical evaluation aspect, the target registration error between the landmark pairs is [Formula: see text] mm. In addition, the clinical application confirms that the reference model can meet clinical requirements. CONCLUSION: To the best of our knowledge, we propose the first CMF reconstruction method considering the global performance of reconstruction and anatomically local evaluation from clinical experience. Simulated experiments and clinical cases prove the general applicability and strength of the method.

[Changes in morphology and steroidogenic function of aged human Leydig cells].

OBJECTIVE: To investigate the changes of morphology and steroidogenic function in aged human Leydig cells and to understand the mechanism of late onset hypogonadism (LOH). METHODS: Ten young and ten aged male subjects were enrolled in this study. AMS (Aging Male's Symptoms) scale was used for symptom evaluation. Testes species with LOH were utilized as the research model. Then the histological changes in testis and ultrastructure of Leydig cells were observed by HE staining and electron microscopy (EM), respectively. The serum total testosterone concentrations were measured by an ELISA kit. The expressions of steroidogenic acute regulatory (StAR) protein and cholesterol-side-chain cleavage enzyme (P450scc) were detected by western blot. RESULTS: The scores of AMS in the aged group were higher than those in the young group with decreased serum testosterone levels (61.25 ± 7.08 vs. 20.75 ± 3.73,P<0.001). And the serum testosterone level of the aged human was lower than that of the young human [(3.12 ± 0.58) µg/L vs. (6.29 ± 1.17) µg/L,P<0.05]. HE staining showed that degenerative changes occurred in the aged human testes. And many swollen mitochondria with mitochondrial cristae that disappeared were found in Leydig cells of the aged human by EM. The serum total testosterone level of the aged human was significantly lower than that of the young group. And the expressions of StAR and P450scc protein in the aged group were significantly lower than those of the young group. CONCLUSION: Mitochondrial swelling and decreased expressions of StAR and P450scc were closely related to the reduced ability of testosterone synthesis in aged males. And the exact mechanism needs further investigation.

Augmented reality navigation for minimally invasive knee surgery using enhanced arthroscopy.

PURPOSE: During the minimally invasive knee surgery, surgeons insert surgical instruments and arthroscopy through small incisions, and implement treatment assisted by 2D arthroscopic images. However, this 2D arthroscopic navigation faces several problems. Firstly, the guidance information is displayed on a screen away from the surgical area, which makes hand/eye coordination difficult. Secondly, the small incision limits the surgeons to view the internal knee structures only from an arthroscopic camera. In addition, arthroscopic images commonly appear obscure visions. METHODS: To solve these problems, we proposed a novel in-situ augmented reality navigation system with the enhanced arthroscopic information. Firstly, intraoperative anatomical locations were obtained by using arthroscopic images and arthroscopy calibration. Secondly, tissue properties-based model deformation method was proposed to update the 3D preoperative knee model with anatomical location information. Then, the updated model was further rendered with glasses-free real 3D display for achieving the global in-situ augmented reality view. In addition, virtual arthroscopic images were generated from the updated preoperative model to provide the anatomical information of the operation area. RESULTS: Experimental results demonstrated that virtual arthroscopic images could reflect the correct structure information with a mean error of 0.32 mm. Compared with 2D arthroscopic navigation, the proposed augmented reality navigation reduced the targeting errors by 2.10 mm and 2.70 mm for the experiments of knee phantom and in-vitro swine knee, respectively. CONCLUSION: Our navigation method is helpful for minimally invasive knee surgery since it can provide the global in-situ information and detail anatomical information.

Tissue Structure Updating for In Situ Augmented Reality Navigation Using Calibrated Ultrasound and Two-Level Surface Warping.

OBJECTIVE: In minimally invasive surgery (MIS), in situ augmented reality (AR) navigation systems are usually implemented using a glasses-free 3D display to represent the preoperative tissue structure, and can provide intuitive see-through guidance information. However, due to changes in intraoperative tissue, the preoperative tissue structure is not able to exactly correspond to reality, which influences the precision of in situ AR navigation. To solve this problem, we propose a method to update the tissue structure for in situ AR navigation in such way to reflect changes in intraoperative tissue. METHODS: The proposed method to update the tissue structure is based on the calibrated ultrasound and two-level surface warping technologies. Firstly, the particle filter-based calibration is implemented to perform ultrasound calibration and obtain intraoperative position of anatomical points. Secondly, intraoperative positions of anatomical points are inputted in the two-level surface warping method to update the preoperative tissue structure. Finally, the glasses-free real 3-D display of the updated tissue structure is finished, and is superimposed onto a patient by a translucent mirror for in situ AR navigation. RESULTS: we validated the proposed method by simulating liver tissue intervention, and achieved the tissue updating accuracy of 92.86%. Furthermore, the targeting error of AR navigation based on the proposed method was also evaluated through minimally invasive liver surgery, and the acquired mean targeting error was 1.92 mm. CONCLUSION: The results demonstrate that the proposed AR navigation method is effective. SIGNIFICANCE: The proposed method can facilitate MIS, as it provides accurate 3D navigation.