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Growth of malignant cells in solid tumors induces changes to the tumor microenvironment (TME). These changes result in promotion of tumor growth, invasion, and metastasis, but also in tumor resistance to drugs and radiotherapy. The enhanced permeability and retention (EPR) effect in neo-angiogenic tumor tissue enables the transport of therapeutic molecules from the circulation into the tumor, but studies show that further diffusion of these agents is often not sufficient for efficient tumor eradication. Despite the hyperpermeable vasculature facilitating the delivery of drugs and tracers, the high density of stromal cells and matrix proteins, in combination with the elevated interstitial fluid pressure in the microenvironment of solid tumors, presents a barrier which limits the delivery of compounds to the core of the tumor. Reversing the cancer-cell-induced changes to the microenvironment as well as novel nanoparticle strategies to circumvent tumor-induced stromal changes have therefore been suggested as potential methods to improve the delivery of therapeutic molecules and drug efficacy. Strategies to modulate the TME, i.e., normalization of tumor vasculature and depletion of excessive stromal proteins and cells, show promising results in enhancing delivery of therapeutic compounds. Modulation of the TME may therefore enhance the efficacy of current cancer treatments and facilitate the development of novel treatment methods as an alternative for invasive resection procedures.

Surgeons are known for their steady hands, decision-making skills, and, according to some, their self-admiration [...]

(1) Background: To better understand the dynamic characteristics of a ball bearing with an elastic ring squeeze film damper (ERSFD) under sudden unbalance, a novel dynamic model was established by fully considering the coupling between the ERSFD, bearing outer ring (the journal), rotor, and disc (loading bearing); (2) Methods: An improved secant method was developed to determine the initial eccentricity values of the bearing’s outer ring and the disc. The dynamic response of the outer ring under different speed ratios, damping ratios, and mass ratios was solved using the variable-step Runge–Kutta method; (3) Results: In comparison, a low-speed ratio, high damping ratio, and low mass ratio were more conducive to suppressing the bearing vibration. When the imbalance was suddenly introduced, the displacement amplitude of the eccentricity, transmissibility, amplitude–frequency response, and the radius of the outer ring center locus increased; (4) Conclusions: This work provides a reference for further studying the nonlinear vibration of rolling bearings coupled with an ERSFD.

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In the process of dynamic unbalance detection for precision cylindrical rollers, challenges such as difficulty in achieving effective driving and susceptibility to surface damage during driving significantly impact the accuracy of unbalance detection. This hinders the industry’s ability to achieve the non-destructive detection of cylindrical rollers. Therefore, this paper proposes a novel driving method to enable non-destructive driving of precision cylindrical rollers. The structural principles of the driving mechanism are presented, and a mechanical model for the cylindrical roller is established to analyze the force distribution. Subsequently, a mathematical model for the air film bearing the cylindrical roller is developed to study the variation characteristics of the air film’s load-bearing capacity. The optimal air film thickness is determined, and the rationality of the mathematical model is validated through simulation analysis. Finally, an experimental platform for non-destructive driving is constructed to further verify the effectiveness of the proposed method. This research provides a prerequisite for the non-destructive detection of dynamic unbalance in precision cylindrical rollers.

Due to the coupling of the damper journal with the elastic ring and oil film, the elastic ring squeeze film damper (ERSFD) shows better dynamic performance in comparison with the traditional squeeze film damper (SFD). Therefore, a novel rigid–elastic–oil coupled mathematical model was established. The elastic ring deformation, as the key point, is solved according to the planar bending theory. Then, based on the pressure governing equation of the oil film, using the central finite difference method, the oil film pressure was addressed. Meanwhile, the Simpson method was implemented to calculate the dynamic characteristic coefficients (equivalent stiffness and damping Ce) of ERSFD (DCCEs). Also, we analyzed the influence of journal eccentricity, oil film radius clearance, flexibility coefficient and damping hole diameter on the DCCEs, and the results were compared and verified with the existing literature. The sensitivity of each parameter to the DCCEs was analyzed by using the linear regression method. According to the results, the flexibility coefficient has the greatest effect on the DCCEs, followed by the oil film radius clearance. The eccentricity of the journal and damping hole diameter have the least impact. This work will provide a theoretical basis for reflecting on the bearing dynamic characteristics more truly and accurately.

Keypoint detection and description play a pivotal role in various robotics and autonomous applications, including Visual Odometry (VO), visual navigation, and Simultaneous Localization And Mapping (SLAM). While a myriad of keypoint detectors and descriptors have been extensively studied in conventional camera images, the effectiveness of these techniques in the context of LiDAR-generated images, i.e., reflectivity and ranges images, has not been assessed. These images have gained attention due to their resilience in adverse conditions, such as rain or fog. Additionally, they contain significant textural information that supplements the geometric information provided by LiDAR point clouds in the point cloud registration phase, especially when reliant solely on LiDAR sensors. This addresses the challenge of drift encountered in LiDAR Odometry (LO) within geometrically identical scenarios or where not all the raw point cloud is informative and may even be misleading. This paper aims to analyze the applicability of conventional image keypoint extractors and descriptors on LiDAR-generated images via a comprehensive quantitative investigation. Moreover, we propose a novel approach to enhance the robustness and reliability of LO. After extracting keypoints, we proceed to downsample the point cloud, subsequently integrating it into the point cloud registration phase for the purpose of odometry estimation. Our experiment demonstrates that the proposed approach has comparable accuracy but reduced computational overhead, higher odometry publishing rate, and even superior performance in scenarios prone to drift by using the raw point cloud. This, in turn, lays a foundation for subsequent investigations into the integration of LiDAR-generated images with LO.

Three frequently encountered problems—a variety of fault types, data with insufficient labels, and missing fault types—are the common challenges in the early fault diagnosis of space flywheel rotor systems. Focusing on the above issues, this paper proposes an intelligent early fault diagnosis method based on the multi-channel convolutional neural network with hierarchical branch and similarity clustering (HB-SC-MCCNN). First, a similarity clustering (SC) method is integrated into the parameter-shared dual MCCNN architecture to set up as the basic structural block. The hierarchical branch model and additional loss are then added to SC-MCCNN to form a hierarchical branch network, which simplifies the problem of fault multi-classification into binary classification with multi-steps. Based on the self-learning characteristics of the proposed model, the unlabeled data and the missing fault types in the training set are re-labeled to realize the re-training of the network. The results of the experiments for comparing the abilities between the proposed method and several advanced deep learning models confirm that on the established early fault dataset of the space flywheel rotor system, the proposed method successfully achieves the hierarchical diagnosis and presents stronger competitiveness in the case of insufficient labeled data and missing fault types at the same time.

This study focuses on the rivet early fatigue characteristics in a deep-groove ball bearing cage for a transmission system in a turboprop engine. Nonlinear dynamic differential equations for the deep-groove ball bearing with a two-piece cage were developed. The rivet stress was used to identify the early failure mechanism of the rivets. This investigation revealed that by delivering an optimal preload of the rivet causes the two halves of the cage have less misalignment and a lower rivet stress. The fit relationship between the rivet and the rivet bore has a significant influence on the rivet stress. Excessive clearance increases the stress on the head of the rivet, while excessive interference increases the stress on the middle of the rivet. For the 1.5 mm diameter rivet analyzed in this study, the appropriate fit relationship is −0.02 mm–0 mm. A reasonable matching value of the load and the speed and the cage clearance ratio are beneficial to reducing the rivet stress. The impact load acting on the bearing and a ring misalignment can increase the rivet stress.

LiDAR-based simultaneous localization and mapping (SLAM) approaches have obtained considerable success in autonomous robotic systems. This is in part owing to the high accuracy of robust SLAM algorithms and the emergence of new and lower-cost LiDAR products. This study benchmarks the current state-of-the-art LiDAR SLAM algorithms with a multi-modal LiDAR sensor setup, showcasing diverse scanning modalities (spinning and solid state) and sensing technologies, and LiDAR cameras, mounted on a mobile sensing and computing platform. We extend our previous multi-modal multi-LiDAR dataset with additional sequences and new sources of ground truth data. Specifically, we propose a new multi-modal multi-LiDAR SLAM-assisted and ICP-based sensor fusion method for generating ground truth maps. With these maps, we then match real-time point cloud data using a normal distributions transform (NDT) method to obtain the ground truth with a full six-degrees-of-freedom (DOF) pose estimation. These novel ground truth data leverage high-resolution spinning and solid-state LiDARs. We also include new open road sequences with GNSS-RTK data and additional indoor sequences with motion capture (MOCAP) ground truth, complementing the previous forest sequences with MOCAP data. We perform an analysis of the positioning accuracy achieved, comprising ten unique configurations generated by pairing five distinct LiDAR sensors with five SLAM algorithms, to critically compare and assess their respective performance characteristics. We also report the resource utilization in four different computational platforms and a total of five settings (Intel and Jetson ARM CPUs). Our experimental results show that the current state-of-the-art LiDAR SLAM algorithms perform very differently for different types of sensors. More results, code, and the dataset can be found at GitHub.

Real-time condition monitoring and fault diagnosis of spindle bearings are critical to the normal operation of the matching machine tool. In this work, considering the interference of random factors, the uncertainty of the vibration performance maintaining reliability (VPMR) is introduced for machine tool spindle bearings (MTSB). The maximum entropy method and Poisson counting principle are combined to solve the variation probability, so as to accurately characterize the degradation process of the optimal vibration performance state (OVPS) for MTSB. The dynamic mean uncertainty calculated using the least-squares method by polynomial fitting, fused into the grey bootstrap maximum entropy method, is utilized to evaluate the random fluctuation state of OVPS. Then, the VPMR is calculated, which is used to dynamically evaluate the failure degree of accuracy for MTSB. The results show that the maximum relative errors between the estimated true value and the actual value of the VPMR are 6.55% and 9.91%, and appropriate remedial measures should be taken before 6773 min and 5134 min for the MTSB in Case 1 and Case 2, respectively, so as to avoid serious safety accidents that are caused by the failure of OVPS.

Introduction: Myxofibrosarcoma (MFS) is the most common soft-tissue sarcoma subtype in elderly patients. Local recurrence (LR) remains a major concern as the lack of intraoperative guidance and an infiltrative growth pattern with long, slender tails hamper surgeons’ ability to achieve adequate resection margins for MFS. Fluorescence-guided surgery (FGS) could overcome this concern by delineating tumor tissue during surgery. One of the most important steps to successful FGS is to define a tumor-specific biomarker that is highly overexpressed in tumor tissue while low or absent in adjacent healthy tissue. The aim of this study is to evaluate the expression of eight previously selected promising biomarkers for FGS in MFS tissue samples with adjacent healthy tissue using immunohistochemistry (IHC). Methods: The following eight biomarkers were stained in seventeen paraffin-embedded MFS samples: tumor endothelial marker-1 (TEM-1, also known as endosialin/CD248), vascular endothelial growth factor receptor-1 (VEGFR-1, also known as Flt-1), vascular endothelial growth factor receptor-2 (VEGFR-2, also known as Flk1), vascular endothelial growth factor-A (VEGF-A), epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), platelet derived growth factor receptor-α (PDGFR-α), and cluster of differentiation 40 (CD40, also known as TNFRSF5). A pathologist specializing in sarcoma annotated the margin between the tumor and adjacent healthy tissue in each MFS tissue sample. Subsequently, we used an objective IHC scoring method to assess and compare the difference in staining intensity between the tumor and adjacent healthy tissue, which is crucial for the use of FGS. Results: TEM-1, VEGF-A, and PDGFR-α stained all MFS tumors, while the other biomarkers did not show expression in all MFS tumors. Ultimately, TEM-1 was identified as the most suitable biomarker for FGS in MFS based on higher tumor-to-background (TBR) staining intensity compared to VEGF-A and PDGFR-α, regardless of preoperative therapy. Conclusion: TEM-1-targeted FGS tracers should be further investigated to optimize MFS treatment.

This paper studies the lubrication characteristics of ball bearings for cryogenic turbopumps. First, the frictional coefficients between 440C and a Ag coating, 440C and solid PTFE (polytetrafluoroethylene), and 440C and a PTFE coating in LN2 (liquid nitrogen) are obtained using a ball-on-disk testing machine under a high sliding speed in the range of 0 to 8 m/s and a high contact stress in the range of 2.5 to 3.5 GPa. Dynamic and power loss models of high-speed and high-load ball bearings are established to study the key factors affecting the heat generation characteristics. In order to verify the correctness of these two theoretical models, a coupled fluid-thermal finite element model is built to evaluate the temperatures of the outer ring under different bearing speeds, which are then proved by experiments with ball bearings for cryogenic turbopumps. The results show that the power loss due to the spinning-sliding of the ball and the churning and drag of LN2 account for more than 80% of the total power loss; the spin-roll ratio of the ball on the inner raceway is a key indicator for this type of ball bearing, and the relatively small radial clearance and contact angle are suggested. Both of the proposed theoretical models have sufficient accuracy and can be used in the performance evaluation and optimization design of bearings.

Vein grafts (VGs) are used to bypass atherosclerotic obstructions and arteriovenous fistulas (AVFs) as vascular access for hemodialysis. Vascular remodeling governs post-interventional arterialization, but may also induce VG and AVF failure. Although the endpoint characteristics of vascular remodeling are known, the in vivo process and the role of blood flow dynamics has not been fully studied. Therefore, here we non-invasively quantify vascular remodeling and blood flow alterations over time in murine VG and AVF models. C57BL/6J (n = 7, chow diet) and atherosclerosis-prone ApoE3*Leiden (n = 7) mice underwent VG surgery. Ultrasound imaging was performed at 3, 7, 14, 21, and 28 days post-surgery. C57BL/6J mice (n = 8) received AVF surgery. Ultrasound imaging was performed at 7 and 14 days post-surgery. The luminal volume increased by 42% in the VGs of C57BL/6J and 38% in the VGs of ApoE3*Leiden mice at 28 days relative to 3 days post-surgery. Longitudinally, an 82% increase in wall volume and 76% increase in outward remodeling was found in the ApoE3*Leiden mice, with a constant wall size in C57BL/6J mice. Proximally, the pulsatility index, resistive index, and peak systolic velocity decreased longitudinally in both groups. Distally, the maximum acceleration increased with 56% in C57BL/6J VGs. Among the AVFs, 50% showed maturation after 7 days, based on a novel flow-criterium of 23 mL/min. Distinct flow patterns were observed at the anastomotic site and inflow artery of the AVFs relative to the control carotid arteries. Vascular remodeling can be quantified by ultra-high-frequency ultrasound imaging over time in complex animal models, via three-dimensional structural parameters and site-specific hemodynamic indices.

Information such as probability distribution, performance degradation trajectory, and performance reliability function varies with the service status of rolling bearings, which is difficult to analyze and evaluate using traditional reliability theory. Adding equipment operation status to evaluate the bearing operation performance status has become the focus of current research to ensure the effective maintenance of the system, reduce faults, and improve quality under the condition of traditional probability statistics. So, a mathematical model is established by proposing the hierarchical maximum entropy Bayesian method (HMEBM), which is used to evaluate the operation performance status of rolling bearings. When calculating the posterior probability density function (PPDF), the similarities between time series regarded as a weighting coefficient are calculated using overlapping area method, membership degree method, Hamming approach degree method, Euclidean approach degree method, and cardinal approach degree method. The experiment investigation shows that the variation degree of the optimal vibration performance status can be calculated more accurately for each time series relative to the intrinsic series.

Molecular imaging of pathologic lesions can improve efficient detection of cancer and cardiovascular diseases. A shared pathophysiological feature is angiogenesis, the formation of new blood vessels. Endoglin (CD105) is a coreceptor for ligands of the Transforming Growth Factor-β (TGF-β) family and is highly expressed on angiogenic endothelial cells. Therefore, endoglin-based imaging has been explored to visualize lesions of the aforementioned diseases. This systematic review highlights the progress in endoglin-based imaging of cancer, atherosclerosis, myocardial infarction, and aortic aneurysm, focusing on positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), near-infrared fluorescence (NIRF) imaging, and ultrasound imaging. PubMed was searched combining the following subjects and their respective synonyms or relevant subterms: “Endoglin”, “Imaging/Image-guided surgery”. In total, 59 papers were found eligible to be included: 58 reporting about preclinical animal or in vitro models and one ex vivo study in human organs. In addition to exact data extraction of imaging modality type, tumor or cardiovascular disease model, and tracer (class), outcomes were described via a narrative synthesis. Collectively, the data identify endoglin as a suitable target for intraoperative and diagnostic imaging of the neovasculature in tumors, whereas for cardiovascular diseases, the evidence remains scarce but promising.

Surgeons rely almost completely on their own vision and palpation to recognize affected tissues during surgery. Consequently, they are often unable to distinguish between different cells and tissue types. This makes accurate and complete resection cumbersome. Targeted image-guided surgery (IGS) provides a solution by enabling real-time tissue recognition. Most current targeting agents (tracers) consist of antibodies or peptides equipped with a radiolabel for Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT), magnetic resonance imaging (MRI) labels, or a near-infrared fluorescent (NIRF) dye. These tracers are preoperatively administered to patients, home in on targeted cells or tissues, and are visualized in the operating room via dedicated imaging systems. Instead of using these ‘passive’ tracers, there are other, more ‘active’ approaches of probe delivery conceivable by using living cells (macrophages/monocytes, neutrophils, T cells, mesenchymal stromal cells), cell(-derived) fragments (platelets, extracellular vesicles (exosomes)), and microorganisms (bacteria, viruses) or, alternatively, ‘humanized’ nanoparticles. Compared with current tracers, these active contrast agents might be more efficient for the specific targeting of tumors or other pathological tissues (e.g., atherosclerotic plaques). This review provides an overview of the arsenal of possibilities applicable for the concept of cell-based tracers for IGS.

Sarcomas are a rare heterogeneous group of malignant neoplasms of mesenchymal origin which represent approximately 13% of all cancers in pediatric patients. The most prevalent pediatric bone sarcomas are osteosarcoma (OS) and Ewing sarcoma (ES). Rhabdomyosarcoma (RMS) is the most frequently occurring pediatric soft tissue sarcoma. The median age of OS and ES is approximately 17 years, so this disease is also commonly seen in adults while non-pleiomorphic RMS is rare in the adult population. The mainstay of all treatment regimens is multimodal treatment containing chemotherapy, surgical resection, and sometimes (neo)adjuvant radiotherapy. A clear resection margin improves both local control and overall survival and should be the goal during surgery with a curative intent. Real-time intraoperative fluorescence-guided imaging could facilitate complete resections by visualizing tumor tissue during surgery. This review evaluates whether non-targeted and targeted fluorescence-guided surgery (FGS) could be beneficial for pediatric OS, ES, and RMS patients. Necessities for clinical implementation, current literature, and the positive as well as negative aspects of non-targeted FGS using the NIR dye Indocyanine Green (ICG) were evaluated. In addition, we provide an overview of targets that could potentially be used for FGS in OS, ES, and RMS. Then, due to the time- and cost-efficient translational perspective, we elaborate on the use of antibody-based tracers as well as their disadvantages and alternatives. Finally, we conclude with recommendations for the experiments needed before FGS can be implemented for pediatric OS, ES, and RMS patients.

Prehabilitation has been postulated as an effective preventive intervention to reduce postoperative complications, particularly for elderly patients with a relatively high risk of complications. To date, it remains to be determined whether prehabilitation increases physical capacity and reduces postoperative complications. The aim of this study was to assess the feasibility of a 4-week multimodal prehabilitation program consisting of a personalized, supervised training program and nutritional intervention with daily fresh protein-rich food for colorectal cancer patients aged over 64 years prior to surgery. The primary outcome was the feasibility of this prehabilitation program defined as ≥80% compliance with the exercise training program and nutritional intervention. The secondary outcomes were the organizational feasibility and acceptability of the prehabilitation program. A compliance rate of ≥80% to both the exercise and nutritional intervention was accomplished by 6 patients (66.7%). Attendance of ≥80% at all 12 training sessions was achieved by 7 patients (77.8%); all patients (100%) attended ≥80% of the available training sessions. Overall, compliance with the training was 91.7%. Six patients (66.7%) accomplished compliance of ≥80% with the nutritional program. The median protein intake was 1.2 (g/kg/d). No adverse events occurred. This multimodal prehabilitation program was feasible for the majority of patients.

Rectal cancer patients with a complete response after neoadjuvant therapy can be monitored with a watch-and-wait strategy. However, regrowth rates indicate that identification of patients with a pathological complete response (pCR) remains challenging. Targeted near-infrared fluorescence endoscopy is a potential tool to improve response evaluation. Promising tumor targets include carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EpCAM), integrin αvβ6, and urokinase-type plasminogen activator receptor (uPAR). To investigate the applicability of these targets, we analyzed protein expression by immunohistochemistry and quantified these by a total immunostaining score (TIS) in tissue of rectal cancer patients with a pCR. CEA, EpCAM, αvβ6, and uPAR expression in the diagnostic biopsy was high (TIS > 6) in, respectively, 100%, 100%, 33%, and 46% of cases. CEA and EpCAM expressions were significantly higher in the diagnostic biopsy compared with the corresponding tumor bed (p < 0.01). CEA, EpCAM, αvβ6, and uPAR expressions were low (TIS < 6) in the tumor bed in, respectively, 93%, 95%, 85%, and 62.5% of cases. Immunohistochemical evaluation shows that CEA and EpCAM could be suitable targets for response evaluation after neoadjuvant treatment, since expression of these targets in the primary tumor bed is low compared with the diagnostic biopsy and adjacent pre-existent rectal mucosa in more than 90% of patients with a pCR.

Background: Targeted image-guided surgery is based on the detection of tumor cells after administration of a radio-active or fluorescent tracer. Hence, enhanced binding of a tracer to tumor tissue compared to healthy tissue is crucial. Various tumor antigens have been evaluated as possible targets for image-guided surgery of breast cancer, with mixed results. Methods: In this study we have evaluated tyrosine kinase receptor EphB4, a member from the Eph tyrosine kinase receptor family, as a possible target for image-guided surgery of breast cancers. Two independent tissue micro arrays, consisting of matched sets of tumor and normal breast tissue, were stained for EphB4 by immunohistochemistry. The intensity of staining and the percentage of stained cells were scored by two independent investigators. Results: Immunohistochemical staining for EphB4 shows that breast cancer cells display enhanced membranous expression compared to adjacent normal breast tissue. The enhanced tumor staining is not associated with clinical variables like age of the patient or stage or subtype of the tumor, including Her2-status. Conclusion: These data suggest that EphB4 is a promising candidate for targeted image-guided surgery of breast cancer, especially for Her2 negative cases.

Targeted image-guided oncologic surgery (IGOS) relies on the recognition of cell surface-associated proteins, which should be abundantly present on tumor cells but preferably absent on cells in surrounding healthy tissue. The transmembrane receptor tyrosine kinase EphA2, a member of the A class of the Eph receptor family, has been reported to be highly overexpressed in several tumor types including breast, lung, brain, prostate, and colon cancer and is considered amongst the most promising cell membrane-associated tumor antigens by the NIH. Another member of the Eph receptor family belonging to the B class, EphB4, has also been found to be upregulated in multiple cancer types. In this study, EphA2 and EphB4 are evaluated as targets for IGOS of colorectal cancer by immunohistochemistry (IHC) using a tissue microarray (TMA) consisting of 168 pairs of tumor and normal tissue. The IHC sections were scored for staining intensity and percentage of cells stained. The results show a significantly enhanced staining intensity and more widespread distribution in tumor tissue compared with adjacent normal tissue for EphA2 as well as EphB4. Based on its more consistently higher score in colorectal tumor tissue compared to normal tissue, EphB4 appears to be a promising candidate for IGOS of colorectal cancer. In vitro experiments using antibodies on human colon cancer cells confirmed the possibility of EphB4 as target for imaging.