Cytoskeleton-modulating nanomaterials and their therapeutic potentials.

The cytoskeleton, an intricate network of protein fibers within cells, plays a pivotal role in maintaining cell shape, enabling movement, and facilitating intracellular transport. Its involvement in various pathological states, ranging from cancer proliferation and metastasis to the progression of neurodegenerative disorders, underscores its potential as a target for therapeutic intervention. The exploration of nanotechnology in this realm, particularly the use of nanomaterials for cytoskeletal modulation, represents a cutting-edge approach with the promise of novel treatments. Inorganic nanomaterials, including those derived from gold, metal oxides, carbon, and black phosphorus, alongside organic variants such as peptides and proteins, are at the forefront of this research. These materials offer diverse mechanisms of action, either by directly interacting with cytoskeletal components or by influencing cellular signaling pathways that, in turn, modulate the cytoskeleton. Recent advancements have introduced magnetic field-responsive and light-responsive nanomaterials, which allow for targeted and controlled manipulation of the cytoskeleton. Such precision is crucial in minimizing off-target effects and enhancing therapeutic efficacy. This review explores the importance of research into cytoskeleton-targeting nanomaterials for developing therapeutic interventions for a range of diseases. It also addresses the progress made in this field, the challenges encountered, and future directions for using nanomaterials to modulate the cytoskeleton. The continued exploration of nanomaterials for cytoskeleton modulation holds great promise for advancing therapeutic strategies against a broad spectrum of diseases, marking a significant step forward in the intersection of nanotechnology and medicine.

Circ_0008571 modulates the phenotype of vascular smooth muscle cells by targeting miR-145-5p in intracranial aneurysms.

BACKGROUND: The dysfunction of human vascular smooth cells (hVSMCs) is significantly connected to the development of intracranial aneurysms (IAs). By suppressing the activity of microRNAs (miRNAs), circular RNAs (circRNAs) participate in IA pathogenesis. Nevertheless, the role of hsa_circ_0008571 in IAs remains unclear. METHODS: circRNA sequencing was used to identify circRNAs from human IA tissues. To determine the function of circ_0008571, Transwell, wound healing, and cell proliferation assays were conducted. To identify the target of circ_0008571, the analyses of CircInteractome and TargetScan, as well as the luciferase assay were carried out. Furthermore, circ_0008571 knockdown and over-expression were performed to investigate its functions in IA development and the underlying molecular mechanisms. RESULTS: Both hsa_circ_0008571 and Integrin beta 8 (ITGB8) were downregulated, while miR-145-5p transcription was elevated in the aneurysm wall of IAs patients compared to superficial temporal artery tissues. In vitro, cell migration and growth were dramatically suppressed after hsa_circ_0008571 overexpression. Mechanistically, has_circ_0008571 could suppress miR-145-5p activity by direct sponging. Moreover, we found that ITGB8 expression and the activation of the TGF-ß-mediated signaling pathway were significantly enhanced. CONCLUSION: The hsa_circ_0008571-miR-145-5p-ITGB8 axis plays an essential role in IA progression.

Singular and Nonsingular Transitions in the Infrared Plasmons of Nearly Touching Nanocube Dimers.

Narrow gaps between plasmon-supporting materials can confine infrared electromagnetic energy at the nanoscale, thus enabling applications in areas such as optical sensing. However, in nanoparticle dimers, the nature of the transition between touching (zero gap) and nearly nontouching (nonzero gap ≲15 nm) regimes is still a subject of debate. Here, we observe both singular and nonsingular transitions in infrared plasmons confined to dimers of fluorine-doped indium oxide nanocubes when moving from touching to nontouching configurations depending on the dimensionality of the contact region. Through spatially resolved electron energy-loss spectroscopy, we find a continuous spectral evolution of the lowest-order plasmon mode across the transition for finite touching areas, in excellent agreement with the simulations. This behavior challenges the widely accepted idea that a singular transition always emerges in the near-touching regime of plasmonic particle dimers. The apparent contradiction is resolved by theoretically examining different types of gap morphologies, revealing that the presence of a finite touching area renders the transition nonsingular, while one-dimensional and point-like contacts produce a singular behavior in which the lowest-order dipolar mode in the touching configuration, characterized by a net induced charge in each of the particles, becomes unphysical as soon as they are separated. Our results provide valuable insights into the nature of dimer plasmons in highly doped semiconductors.

Clinical Outcomes On Tubridge Flow Diverter in Treatmenting Intracranial Aneurysms: a Retrospective Multicenter Registry Study.

PURPOSE: In China, the application of nitinol Tubridge flow diverter (TFD) has become popular for treating intracranial aneurysms (IAs). In this study, we investigated the safety outcomes of the application of TFD for treating IAs in real-world scenarios. METHODS: We retrospectively analyzed aneurysms treated with TFD in 235 centers throughout China between April 2018 and April 2020. The primary endpoint was the event-free survival rate at 12 months, defined as the occurrence of morbidity (spontaneous rupture, intraparenchymal hemorrhage (IPH), ischemic stroke, and permanent cranial neuropathy) or death. Univariate and multivariate analyses were performed to assess the risk factors. A good outcome was defined as a modified Rankin Score (mRS) of 0-2. RESULTS: We included 1281 unruptured aneurysms treated with TFD. The overall neurological morbidity and death rates after 12 months were 5.4 and 2.8%, respectively. Ischemic strokes were the most common complication (4.2%, P < 0.001). Cranial neuropathy, IPH, and spontaneous rupture occurred in 0.3%, 0.3%, and 0.5% of aneurysms, respectively. Univariate and multivariate analyses indicated that the male gender, older age, larger aneurysm diameter, and aneurysm located on BA were the independent risk factors for neurologic events. Aneurysm located on BA was the independent risk factor for ischemic strokes. Most patients (1222) had access to the mRS, and 93.2% of them achieved good outcomes. CONCLUSION: Treatment of IAs with TFD was associated with low morbidity and mortality, most of which were ischemic events. Large posterior aneurysms might be associated with a higher complication rate. TRIAL REGISTRATION: Retrospectively registered.

Nomograms for assessing the rupture risk of anterior choroid artery aneurysms based on clinical, morphological, and hemodynamic features.

Background and purpose: A notable prevalence of subarachnoid hemorrhage is evident among patients with anterior choroidal artery aneurysms in clinical practice. To evaluate the risk of rupture in unruptured anterior choroidal artery aneurysms, we conducted a comprehensive analysis of risk factors and subsequently developed two nomograms. Methods: A total of 120 cases of anterior choroidal artery aneurysms (66 unruptured and 54 ruptured) from 4 medical institutions were assessed utilizing computational fluid dynamics (CFD) and digital subtraction angiography (DSA). The training set, consisting of 98 aneurysms from 3 hospitals, was established, with an additional 22 cases from the fourth hospital forming the external validation set. Statistical differences between the two data sets were thoroughly compared. The significance of 9 clinical baseline characteristics, 11 aneurysm morphology parameters, and 4 hemodynamic parameters concerning aneurysm rupture was evaluated within the training set. Candidate selection for constructing the nomogram models involved regression analysis and variance inflation factors. Discrimination, calibration, and clinical utility of the models in both training and validation sets were assessed using area under curves (AUC), calibration plots, and decision curve analysis (DCA). The DeLong test, net reclassification index (NRI), and integrated discrimination improvement (IDI) were employed to compare the effectiveness of classification across models. Results: Two nomogram models were ultimately constructed: model 1, incorporating clinical, morphological, and hemodynamic parameters (C + M + H), and model 2, relying primarily on clinical and morphological parameters (C + M). Multivariate analysis identified smoking, size ratio (SR), normalized wall shear stress (NWSS), and average oscillatory shear index (OSIave) as optimal candidates for model development. In the training set, model 1 (C + M + H) achieved an AUC of 0.795 (95% CI: 0.706 ~ 0.884), demonstrating a sensitivity of 95.6% and a specificity of 54.7%. Model 2 (C + M) had an AUC of 0.706 (95% CI: 0.604 ~ 0.808), with corresponding sensitivity and specificity of 82.4 and 50.3%, respectively. Similarly, AUCs for models 1 and 2 in the external validation set were calculated to be 0.709 and 0.674, respectively. Calibration plots illustrated a consistent correlation between model evaluations and real-world observations in both sets. DCA demonstrated that the model incorporating hemodynamic parameters offered higher clinical benefits. In the training set, NRI (0.224, p = 0.007), IDI (0.585, p = 0.002), and DeLong test (change = 0.089, p = 0.008) were all significant. In the external validation set, NRI, IDI, and DeLong test statistics were 0.624 (p = 0.063), 0.572 (p = 0.044), and 0.035 (p = 0.047), respectively. Conclusion: Multidimensional nomograms have the potential to enhance risk assessment and patient-specific treatment of anterior choroidal artery aneurysms. Validated by an external cohort, the model incorporating clinical, morphological, and hemodynamic features may provide improved classification of rupture states.

Gekko Coil System for Intracranial Aneurysms Treatment in China (GREAT-China): A Prospective Randomized Controlled Open-Label Noninferiority Trial.

OBJECTIVE: This study aimed to evaluate the safety and efficacy of the Gekko coil system in treating intracranial aneurysms (IAs) in clinical practice. METHODS: A prospective multicenter randomized open-label parallel positive control noninferiority trial was conducted by 11 centers in China. Patients with a target IA were randomized 1:1 to coiling with either Gekko or Axium coils. The primary outcome was successful aneurysm occlusion at 6 months postoperative follow-up, whereas the secondary outcomes included the successful occlusion aneurysm rate in the immediate postoperative period, recanalization rate at the 6 months follow-up, and technical success and security. RESULTS: Between May 2018 and September 2020, 256 patients were enrolled and randomized. Per-protocol analysis showed that the successful aneurysm occlusion rate at 6 months was 96.08% for the Gekko coil group compared with 96.12% in the Axium coil group, with a difference of -0.04% (P = 0.877). The successful immediate aneurysm occlusion rates were 86.00% and 77.45% in the Gekko coil group and the Axium coil group, respectively, showing no significant difference between the 2 groups (P = 0.116), whereas the recanalization rates during the 6 months follow-up were 2.02% and 1.96% in the Gekko and Axium coil groups, respectively, which was not statistically significant (P = 1.000). CONCLUSIONS: This trial showed that the Gekko coil system was noninferior to the Axium coil system in terms of efficacy and safety for IA embolization. In clinical practice, the Gekko coil system can be considered safe and effective for treating patients with IA.

Predictors of Perioperative Complications During Leo Baby Stent Treatment for Acutely Ruptured Intracranial Aneurysms: A Retrospective Multicenter Study.

BACKGROUND AND OBJECTIVES: Stent-assisted coiling (SAC) of acutely ruptured aneurysms has been controversial. Moreover, for aneurysms originating from small diameter vessels, the SAC presents more challenges. This study aimed to investigate the predictors of perioperative complications after SAC with Leo baby stent of acutely ruptured aneurysms. METHODS: We performed a retrospective multicenter analysis of 425 patients with acutely ruptured aneurysms treated with Leo baby. We compared clinical characteristics and outcomes among patients with perioperative complications and those without. Subgroup analysis, including thromboembolic and hemorrhagic complications, was also performed. RESULTS: Immediate postoperative angiograms showed Raymond 1 in 357 aneurysms (84.2%), 2 in 53 (12.5%), and 3 in 14 (3.3%). A total of 372 patients (87.5%) were independent (modified Rankin Scale [mRS] score 0-2) at discharge. Perioperative complications occurred in 18 cases (4.2%) harboring 13 cases (3.1%) of thromboembolic complications and 5 cases (1.2%) of hemorrhagic complications. Patients with perioperative complications had a higher rate of unfavorable outcomes at discharge (P = .018), especially with thromboembolic complications (P = .043). Multivariate analysis showed that higher preoperative mRS score (P = .004), irregular shape (P = .017), and larger aneurysms (P = .049) were independent predictors of the overall complications, whereas higher preoperative mRS score (P = .022) was an independent predictor for ischemic complications. The follow-up angiogram was available for 245 patients, and the follow-up angiograms revealed Raymond 1 in 223 aneurysms (91.0%), 2 in 19 (7.8%), and 3 in 3 (1.2%). CONCLUSION: Worse clinical condition, irregular shape, and larger aneurysms were independently associated with overall complications, whereas worse clinical condition was viewed as an independent predictor for thromboembolic complications. Attention to these factors is essential for the safe treatment and prognosis of patients with acutely ruptured aneurysms.

RNA Nanomedicine: Delivery Strategies and Applications.

Delivery of RNA using nanomaterials has emerged as a new modality to expand therapeutic applications in biomedical research. However, the delivery of RNA presents unique challenges due to its susceptibility to degradation and the requirement for efficient intracellular delivery. The integration of nanotechnologies with RNA delivery has addressed many of these challenges. In this review, we discuss different strategies employed in the design and development of nanomaterials for RNA delivery. We also highlight recent advances in the pharmaceutical applications of RNA delivered via nanomaterials. Various nanomaterials, such as lipids, polymers, peptides, nucleic acids, and inorganic nanomaterials, have been utilized for delivering functional RNAs, including messenger RNA (mRNA), small interfering RNA, single guide RNA, and microRNA. Furthermore, the utilization of nanomaterials has expanded the applications of functional RNA as active pharmaceutical ingredients. For instance, the delivery of antigen-encoding mRNA using nanomaterials enables the transient expression of vaccine antigens, leading to immunogenicity and prevention against infectious diseases. Additionally, nanomaterial-mediated RNA delivery has been investigated for engineering cells to express exogenous functional proteins. Nanomaterials have also been employed for co-delivering single guide RNA and mRNA to facilitate gene editing of genetic diseases. Apart from the progress made in RNA medicine, we discuss the current challenges and future directions in this field.

External cold atmospheric plasma-responsive on-site hydrogel for remodeling tumor immune microenvironment.

Although immunotherapy has recently emerged as a promising anti-tumor approach, it remains limited by the immunosuppressive tumor microenvironment. Cold atmospheric plasma irradiation can generate reactive oxygen species and trigger the presentation of tumor-associated antigens. Here, we exploited cold atmospheric plasma for on-site hydrogel application in the tumor environment, aiming to facilitate the sustainable uptake of tumor-associated antigens and nanoadjuvants by dendritic cells. Hyaluronic acid-tyramine conjugate was intratumorally injected as a liquid and formed an on-site hydrogel under irradiation with cold atmospheric plasma. Intratumoral delivery of hyaluronic acid-tyramine conjugate with transforming growth factor ß-blocking nanoadjuvant (TLN) followed by cold atmospheric plasma irradiation yielded a micro-network of TLN-loaded hydrogel (TLN@CHG). In vivo intratumoral injection of TLN@CHG promoted the activation of dendritic cells and more effectively increased the proportion of CD4 T cells and CD8 T cells in the tumor microenvironment, compared to the groups receiving TLN or hydrogel alone. Moreover, in CT26 tumor model mice, cold atmospheric plasma-induced TLN@CHG therapy ablated the primary tumor and provided 100% survival among mice rechallenged with CT26 cells. Taken together, our findings suggest that an on-site hydrogel-based micro-network of TLN has the potential to remodel the tumor immune microenvironment. Although we used TLN in this study, the concept could be extended to support the sustained action of other nanoadjuvants in a hydrogel micro-network.

Predictors of recurrence and complications for the endovascular treatment of unruptured middle cerebral artery aneurysm: A high-volume center experience over 12 years.

OBJECT: To assess the safety and efficacy of endovascular treatment (EVT) of unruptured middle cerebral artery (MCA) aneurysms in a retrospective cohort in a high-volume center. Predictors of complications and recurrence were determined. METHODS: Retrospectively reviewed our database of prospectively collected information for all patients with unruptured MCA aneurysms that were treated by endovascular approach from March 2008 to December 2020. A multivariate analysis was conducted to identify predictors of complications and recurrence. RESULTS: Three hundred and fifty-one patients with 370 unruptured MCA aneurysms underwent EVT were included in this study. Seventy-three aneurysms (19.7%) were treated by coiling without stent, 297 (80.3%) with stent-assisted coiling. The procedures were performed with a technical success rate of 100%. Procedure-related neurological complications occurred in 15 patients (4.1%), including 1 patient died from post-procedural stent thrombosis. Age ≥ 65 years (P = 0.039; OR = 3.400; 95% CI, 1.065-10.860) and aneurysm size ≥ 5 mm (P = 0.009; OR = 15.524; 95% CI, 1.988-121.228) were significantly associated with ischemic complications of EVT. Three hundred and six aneurysms were (87.2%) completed image follow-up (235 DSA and 71 CE-MRA). The median angiographic follow-up time were 7.0 ± 4.3 months (range from 1 to 88 months). Follow-up angiograms showed that 249 aneurysms (81.4%) were completed occluded, 29 aneurysms (9.5%) were improved, 17 aneurysms (5.6%) were stable, and 11 aneurysms (3.6%) were recanalized and 10 of them accepted retreatments. Aneurysm size ≥ 10 mm was a predictor of recanalization (P = 0.004; OR = 11.213; 95% CI, 2.127-59.098) and stent-assisted coiling can significantly reduce recanalization (P = 0.004; OR = 0.105; 95% CI, 0.023-0.479). CONCLUSIONS: EVT is a safe and effective therapeutics for unruptured MCA aneurysms management, and provides durable aneurysm occlusion rate during follow-up. Large MCA aneurysms have higher recurrence and ischemic complications risk after EVT. Stent-assisted coiling can significantly reduce the recurrence rate without increasing the risk of complications.

Tolerogenic Nanovaccine for Prevention and Treatment of Autoimmune Encephalomyelitis.

Herein, a tolerogenic nanovaccine is developed and tested on an animal model of multiple sclerosis. The nanovaccine is constructed to deliver the self-antigen, myelin oligodendrocyte glycoprotein (MOG) peptide, and dexamethasone on an abatacept-modified polydopamine core nanoparticle (AbaLDPN-MOG). AbaLDPN-MOG can target dendritic cells and undergo endocytosis followed by trafficking to lysosomes. AbaLDPN-MOG blocks the interaction between CD80/CD86 and CD28 in antigen-presenting cells and T cells, leading to decreased interferon gamma secretion. The subcutaneous administration of AbaLDPN-MOG to mice yields significant biodistribution to lymph nodes and, in experimental-autoimmune encephalomyelitis (EAE) model mice, increases the integrity of the myelin basic sheath and minimizes the infiltration of immune cells. EAE mice are treated with AbaLDPN-MOG before or after injection of the autoantigen, MOG. Preimmunization of AbaLDPN-MOG before the injection of MOG completely blocks the development of clinical symptoms. Early treatment with AbaLDPN-MOG at three days after injection of MOG also completely blocks the development of symptoms. Notably, treatment of EAE symptom-developed mice with AbaLDPN-MOG significantly alleviates the symptoms, indicating that the nanovaccine has therapeutic effects. Although AbaLDPN is used for MOG peptide delivery in the EAE model, the concept of AbaLDPN can be widely applied for the prevention and alleviation of other autoimmune diseases.

Nanomaterials for antigen-specific immune tolerance therapy.

Impairment of immune tolerance might cause autologous tissue damage or overactive immune response against non-pathogenic molecules. Although autoimmune disease and allergy have complicated pathologies, the current strategies have mainly focused on symptom amelioration or systemic immunosuppression which can lead to fatal adverse events. The induction of antigen-specific immune tolerance may provide therapeutic benefits to autoimmune disease and allergic response, while reducing nonspecific immune adverse responses. Diverse nanomaterials have been studied to induce antigen-specific immune tolerance therapy. This review will cover the immunological background of antigen-specific tolerance, clinical importance of antigen-specific immune tolerance, and nanomaterials designed for autoimmune and allergic diseases. As nanomaterials for modulating immune tolerances, lipid-based nanoparticles, polymeric nanoparticles, and biological carriers have been covered. Strategies to provide antigen-specific immune tolerance have been addressed. Finally, current challenges and perspectives of nanomaterials for antigen-specific immune tolerance therapy will be discussed.

Stent-assisted coiling vs. coiling alone of ruptured tiny intracranial aneurysms: A contemporary cohort study in a high-volume center.

Objective: This study aims to compare the safety and efficacy of stent-assisted coiling (SAC) with those of coiling alone (CA) for the treatment of ruptured tiny intracranial aneurysms. Methods: We enrolled 245 patients with ruptured tiny intracranial aneurysms treated with coil embolization. Patients were grouped into SAC and CA groups. Baseline characteristics, periprocedural complications, clinical outcomes, and angiographic results were compared between the two groups. In addition, a subgroup analysis was conducted in the SAC group, and patients were regrouped into low-profile visualized intraluminal support (LVIS) and laser-cut groups to compare the perioperative procedure-related complications and clinical and angiographic follow-up outcomes. Results: All baseline characteristics were equivalent between the two groups except for aneurysm size and dome-to-neck aspect ratio. The rates of overall procedure-related complications, intraprocedural rupture, postoperative early rebleeding, intraprocedural thrombosis, postprocedural thrombosis, and procedure-related mortality were comparable between the two groups (P = 0.105, 0.145, 0.308, 1.000, 1.000, 0.160, respectively). Nevertheless, the rate of hemorrhagic complication in the SAC group was significantly higher (P = 0.023). The angiographic follow-up outcomes showed that the SAC group had a higher complete occlusion rate and lower recurrence rate (88.2 vs. 67.1%, 5.4 vs. 15.2%, P = 0.001). The clinical outcomes at discharge and follow-up between the two groups demonstrated no significant differences (P = 0.192 and P = 0.085, respectively). For subgroup analysis, LVIS stents were associated with a significantly higher rate of complete occlusion (P = 0.014) and a lower rate of intraprocedural rupture (p = 0.021). Moreover, multivariate analysis showed that there were no predictors for the overall, hemorrhagic, and ischemic procedure-related complications, while Raymond class was an independent predictor of retreatment (OR = 3.508, 95% CI 1.168-11.603; P = 0.029). Conclusion: Stent-assisted coiling may increase the incidence of hemorrhagic events with favorable angiographic results and comparable clinical outcomes compared with stand-alone coiling. Nevertheless, LVIS stent could improve the safety compared with lazer-cut stent. Simultaneously, considering the better long-term effect, LVIS stent-assisted coiling may be a preferable choice for ruptured tiny intracranial aneurysms.

Retreatment with a flow diverter for recurrent blood blister-like aneurysms after embolization: A single-center case series.

Background and purpose: Treatment of blood blister-like aneurysms (BBAs) has been a significant challenge mainly due to their high recurrence rate even after stent-assisted coiling (SAC) embolization. This study aims to evaluate the safety and efficacy of treating recurrent BBAs after SAC with a flow diverter (FD). Methods: A retrospective series of patients with recurrent BBAs who underwent the retreatment with the FD from June 2018 to December 2021 was included to analyze perioperative safety and immediate postoperative and follow-up outcomes. Results: The study enrolled 13 patients with recurrent BBAs previously treated with SAC. Within previous stents, an FD was deployed for retreatment, including eight Tubridge FDs and five PEDs. The time interval between initial treatment and FD implantation was 14-90 days. A total of 11 cases were treated with a single FD alone; two cases were treated with further endovascular coiling embolization, followed by FD implantation. The angiographic follow-up (6-12 months) was available in 12 patients, and all 12 recurrent BBAs were completely occluded. No perioperative complication was detected, and no rebleeding was found during the clinical follow-up (6-36 months). Conclusion: The use of the FD to manage recurrent BBAs after SAC is technically feasible, safe, and effective. The key to the success of the procedure is to ensure that the FD stent is fully open and has good apposition with the previously implanted stent.

Using closed-circuit television cameras to analyze traffic safety at intersections based on vehicle key points detection.

In the within-intersection area, vehicles from different approaches make turning movements resulting in many conflict points. Hence, drivers are more prone to make mistakes in that area, which leads to severe crash outcomes. In the current roadway system, the Closed-Circuit Television (CCTV) cameras could be a cost-effective sensor to monitor the safety condition in the within-intersection area. This study proposed a framework named "Near Miss Event Detection System (NMEDS)" for road safety diagnostics using video data collected from CCTV cameras. The proposed framework combined the Mask-RCNN bounding box detection and Occlusion-Net detection algorithm to reconstruct vehicles' key points in a 3D view. Vehicles' key points including right-front headlight, left-front headlight, right-back taillight, and left-back taillight could be identified and transformed into a 2D bird's-eye view (i.e., real-world coordinate system) for safety analysis. A method was proposed to modify the occluded key points, which could not be observed by cameras due the turning movements in the within-intersection area. The post-encroachment time (PET) was calculated by using the trajectory data in the 2D view. The proposed framework was compared with two counterparts (i.e., bounding box detection only and key point detection only) by conducting an empirical study at a 4-leg intersection. The results suggested that the proposed framework could obtain more accurate vehicle trajectory and better autocorrelation analytics was conducted to identify the significantly dangerous locations in the within-intersection area. It is expected that the proposed methods could help diagnose road safety problems using CCTV cameras. Moreover, the proposed method could be incorporated with Connected Vehicle Systems and provide information to nearby drivers based on Infrastructure-to-Vehicle (I2V) technologies.

Evaluation of automated emergency braking system's avoidance of pedestrian crashes at intersections under occluded conditions within a virtual simulator.

Pedestrians' red-light crossing can present a threat to themselves and the safety at intersections, especially for the through vehicles since their speeds are higher compared to the turning vehicles. The automated emergency braking (AEB) system could actively detect pedestrians and react to avoid potential conflicts. This study contributes to evaluate the effectiveness of the AEB system under occlusion conditions. The braking algorithm was developed in the virtual simulator CARLA to control the ego vehicle. Three occlusion scenarios in which the sensor of the AEB system could not detect the pedestrian if the pedestrian is occluded by a stopping vehicle. The evaluation experiments were conducted at a typical 4-leg intersection considering different motion statuses of the ego vehicle and pedestrian. The effects of field of view (FOV) of the sensor and activation threshold of the AEB system were also explored. The study indicated that the effectiveness of the AEB system could be reduced by the occlusion time. A longer activation threshold is recommended if the pedestrian is potentially occluded for a long time. The effects of other factors such as the speed of the ego vehicle and pedestrian and scenarios were also identified.

On-demand delivery of protein drug from 3D-printed implants.

Here, we constructed 3D-printed multiunit implants to enable remote light-controlled protein drug delivery in a spatiotemporal manner. Multiunit implants were designed to be 3D printed using polycaprolactone, lauric acid, and melanin as a matrix, and a polycaprolactone scaffold as a multiunit divider. As a model drug, insulin was loaded to each unit of the implant. The 3D printing yielded a rectangular matrix with multiunit sectors segregated by polycaprolactone lanes. Irradiation with near infrared light (NIR) triggered controlled release of insulin from the irradiated locus: Upon NIR irradiation, heat generated from the melanin melted the polycaprolactone/lauric acid matrix to release insulin from the scaffold. In the absence of melanin in the matrix, the implant did not show NIR-responsive insulin release. When lauric acid was absent from the matrix, the NIR-irradiated unit did not undergo dismantling. When the insulin-loaded multiunit implant was applied to a mouse diabetic model and irradiated with NIR, repetitive insulin release resulted in an efficient decrease of the blood glucose level over multiple days. Together, these results suggest that 3D printing technology-based multi-dosing of insulin on demand can enable convenient treatment of diabetes through external NIR irradiation, potentially avoiding the pain and discomfort of repeated insulin injections.

Artificial intelligence (AI) versus expert: A comparison of left ventricular outflow tract velocity time integral (LVOT-VTI) assessment between ICU doctors and an AI tool.

PURPOSE: The application of point of care ultrasound (PoCUS) in medical education is a relatively new course. There are still great differences in the existence, quantity, provision, and depth of bedside ultrasound education. The left ventricular outflow tract velocity time integral (LVOT-VTI) has been successfully used in several studies as a parameter for hemodynamic management of critically ill patients, especially in the evaluation of fluid responsiveness. While LVOT-VTI has been broadly used, valuable applications using artificial intelligence (AI) in PoCUS is still limited. We aimed to identify the degree of correlation between auto LVOT-VTI and the manual LVOT-VTI acquired by PoCUS trained ICU doctors. METHODS: Among the 58 ICU doctors who attended PoCUS training from 1 September 2019 to 30 November 2020, 46 ICU doctors who trained for more than 3 months were enrolled. At the end of PoCUS training, each of the enrolled ICU doctors acquired echocardiography parameters of a new ICU patient in 2 h after new patient was admitted. One of the two bedside expert sonographers would take standard echocardiogram of new ICU patients within 24 h. For ICU doctors, manual LVOT-VTI was obtained for reference and auto LVOT-VTI was calculated instantly by using an AI software tool. Based on the image quality of the auto LVOT-VTI, ICU patients was separated into ideal group (n = 31) and average group (n = 15). RESULTS: Left ventricular end-diastolic dimension (LVEDd, p = 0.1028), left ventricular ejection fraction (LVEF, p = 0.3251), left atrial dimension (LA-d, p = 0.0962), left ventricular E/A ratio (p = 0.160), left ventricular wall motion (p = 0.317) and pericardial effusion (p = 1) had no significant difference between trained ICU doctors and expert sonographer. ICU patients in average group had greater sequential organ failure assessment (SOFA) score (7.33 ± 1.58 vs. 4.09 ± 0.57, p = 0.022) and lactic acid (3.67 ± 0.86 mmol/L vs. 1.46 ± 0.12 mmol/L, p = 0.0009) with greater value of LVEDd (51.93 ± 1.07 vs. 47.57 ± 0.89, p = 0.0053), LA-d (39.06 ± 1.47 vs. 35.22 ± 0.98, p = 0.0334) and percentage of decreased wall motion (p = 0.0166) than ideal group. There were no significant differences of δLVOT-VTI (|manual LVOT-VTI - auto LVOT-VTI|/manual VTI*100%) between the two groups (8.8% ± 1.3% vs. 10% ± 2%, p = 0.6517). Statistically, significant correlations between manual LVOT-VTI and auto LVOT-VTI were present in the ideal group (R2  = 0.815, p = 0.00) and average group (R2  = 0.741, p = 0.00). CONCLUSIONS: ICU doctors could achieve the satisfied level of expertise as expert sonographers after 3 months of PoCUS training. Nearly two thirds of the enrolled ICU doctors could obtain the ideal view and one third of them could acquire the average view. ICU patients with higher SOFA scores and lactic acid were less likely to acquire the ideal view. Manual and auto LVOT-VTI had statistically significant agreement in both ideal and average groups. Auto LVOT-VTI in ideal view was more relevant with the manual LVOT-VTI than the average view. AI might provide real-time guidance among novice operators who lack expertise to acquire the ideal standard view.

The Prediction of Preterm Birth Using Time-Series Technology-Based Machine Learning: Retrospective Cohort Study.

BACKGROUND: Globally, the preterm birth rate has tended to increase over time. Ultrasonography cervical-length assessment is considered to be the most effective screening method for preterm birth, but routine, universal cervical-length screening remains controversial because of its cost. OBJECTIVE: We used obstetric data to analyze and assess the risk of preterm birth. A machine learning model based on time-series technology was used to analyze regular, repeated obstetric examination records during pregnancy to improve the performance of the preterm birth screening model. METHODS: This study attempts to use continuous electronic medical record (EMR) data from pregnant women to construct a preterm birth prediction classifier based on long short-term memory (LSTM) networks. Clinical data were collected from 5187 pregnant Chinese women who gave birth with natural vaginal delivery. The data included more than 25,000 obstetric EMRs from the early trimester to 28 weeks of gestation. The area under the curve (AUC), accuracy, sensitivity, and specificity were used to assess the performance of the prediction model. RESULTS: Compared with a traditional cross-sectional study, the LSTM model in this time-series study had better overall prediction ability and a lower misdiagnosis rate at the same detection rate. Accuracy was 0.739, sensitivity was 0.407, specificity was 0.982, and the AUC was 0.651. Important-feature identification indicated that blood pressure, blood glucose, lipids, uric acid, and other metabolic factors were important factors related to preterm birth. CONCLUSIONS: The results of this study will be helpful to the formulation of guidelines for the prevention and treatment of preterm birth, and will help clinicians make correct decisions during obstetric examinations. The time-series model has advantages for preterm birth prediction.

Low profile visualized intraluminal support stent-assisted Hydrocoil embolization for acutely ruptured wide-necked intracranial aneurysms: A propensity score-matched cohort study.

PURPOSE: To compare the safety and efficacy of low profile visualized intraluminal support (LVIS) stent-assisted hydrogel coil embolization and LVIS stent-assisted bare platinum coil embolization for acutely ruptured wide-necked intracranial. METHODS: 89 patients who underwent LVIS stent-assisted hydrogel coil embolization (hydrogel coil group) and 145 patients who underwent LVIS stent-assisted bare platinum coil embolization (platinum coil group) were retrospectively reviewed after 1:2 propensity score matching (PSM). Procedure-related complications, clinical and angiographic follow-up outcomes were compared between the two groups. RESULTS: All baseline characteristics were equivalent between hydrogel coil group and platinum coil group after PSM. There were no statistical differences in immediate postoperative embolization results, clinical and angiographic follow-up outcomes between the two groups (P = 0.514, P = 0.323 and P = 0.949, respectively). Intraprocedural aneurysm rupture, intraprocedural thrombosis and postprocedural thrombosis occurred in 2 patients (2.2%, 2/89), 1 patient (1.1%, 1/89) and 1 patient (1.1%, 1/89) of the hydrogel coil group compared with 1 patient (0.7%, 1/145), 1 patient (0.7%, 1/145) and 2 patients (1.4%, 2/145) of the platinum coil group, respectively (P = 0.559, P = 1.000 and P = 1.000). Nevertheless, the rate of postprocedural aneurysm early rebleeding in the hydrogel coil group was significantly lower than that in the platinum coil group (0.0% vs 4.8%, P = 0.046). CONCLUSION: LVIS stent-assisted hydrogel coil embolization may reduce the risk of aneurysm early rebleeding compared with LVIS stent-assisted bare platinum coil embolization for the treatment of acutely ruptured wide-necked intracranial aneurysms, which implies that hydrogel coil may improve the safety of stent placement for ruptured intracranial aneurysms.