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A novel control method called dynamic straight-right lane (DSRL) control design is proposed for signalised intersections. This design aims to utilise the resources of the right-turn lane to increase the capacity for straight-through traffic while minimising the impact on right-turn vehicles. In this paper, an alternative approach to DSRL control design for T-shaped intersections is proposed. By redesigning the spatial and temporal allocation at the entrance, this design ensures the safety of lane change manoeuvres and reduces the design threshold for T-shaped intersections. To facilitate the implementation of the DSRL control design, a cellular automata model is constructed. Additionally, a case study is conducted, leading to the identification of the optimal design parameters for DSRL control. The proposed DSRL control design is compared with two conventional control designs, namely dedicated right-turn lane control design and static straight-right lane control design, in various geometric and traffic demand scenarios. The findings reveal that the T-shaped intersection, when equipped with a dedicated right-turn lane control design, can achieve a maximum delay optimisation rate of 91% by adopting the DSRL control design. Similarly, the T-shaped intersection, with a static straight-right lane control design, can attain a maximum delay optimisation rate of 84% when employing the DSRL control design.

ObjectiveWe performed this pooled analysis for the first time to comprehensively explore the prognostic value of tumor-associated high endothelial venules (TA-HEVs) and determine their relationships with clinicopathological features in solid tumors.MethodsFour online databases, including PubMed, Web of Science, Embase, and Cochrane Library, were comprehensively searched to identify studies assessing the effect of TA-HEVs on prognosis or clinicopathological features. Hazard ratios (HRs) with 95% confidence intervals (CIs) were applied to evaluate survival outcomes, including overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and cancer-specific survival (CSS). The association between TA-HEV status and clinicopathological characteristics was assessed by odds ratios (ORs) combined with 95% CIs. Subgroup analysis was conducted to explore sources of heterogeneity. The sensitivity analysis was performed to evaluate the stability of our findings. Meanwhile, Funnel plots were employed to visually evaluate potential publication bias, and both Begg’s and Egger’s tests were adopted to quantitatively determine publication bias.ResultsA total of 13 retrospective cohort studies, involving 1,933 patients were finally included in this meta-analysis. Effect-size pooling analysis showed that the positivity of TA-HEVs was related to improved OS (pooled HR: 0.75, 95% CI: 0.62-0.93, P

While consensus on single-incision laparoscopic appendectomy (SILA) for acute appendicitis is lacking, our meta-analysis evaluated the safety and efficacy of SILA compared to conventional three-port laparoscopic appendectomy (CTLA). A computer-based search was conducted in the China National Knowledge Infrastructure (CNKI), VIP, Wanfang, China Biological Medicine (CBM), PubMed, Embase, and Cochrane Library databases to identify randomized controlled trials (RCTs) comparing SILA with CTLA groups. Meta-analysis was performed using RevMan 5.3 software. A total of 26 RCTs were included. The meta-analysis results indicated that, compared to the CTLA group, the SILA group had a longer operation time [MD = 7.97, 95 % CI (5.84, 10.10), P

Objective To investigate the resource allocation status of blood testing laboratories in 14 blood stations in Gansu Province, explore the impact of differences in basic conditions on the comprehensive testing ability of laboratories, so as to promote the homogenization and standardization of blood screening capacity in blood stations in Gansu and improve blood safety and effectivenes. Methods An evaluation index system of laboratory resource allocation was constructed and a question-naire was designed. The data of human resources, infrastructure and key equipment of 14 blood stations were collected. The entropy weight -TOPSIS method was used to evaluate and rank the resource allocation of 14 blood stations. Results In the comprehensive evaluation of blood testing laboratory resource allocation in 14 blood stations in Gansu, the top three were laboratories A, B and I, and the last three were laboratories G, M and J. On the whole, the main issue was unreasonable structure of human resources: most laboratories had unreasonable age structure; except for Laboratory A, there was no personnel with bachelor's degree or above in laboratories; most laboratories had not established a team with intermediate professional titles. In terms of infrastructure, the size of seven laboratories could not meet the needs of modern laboratory testing, and all eight blood stations had no spare nucleic acid laboratories nor a mutual spare laboratory with other blood stations As for the key equipment, 5 laboratories had no automatic blood grouping diagnostic instrument, 5 laboratories only had one set of enzyme immunoassay detection system, 3 laboratories had no spare equipment for the key equipment, which means if the equipment failure could not be repaired in time, the release of results would be affected. Conclusion There were significant differences in human resources, infrastructure and key equipment of blood testing laboratories in 14 blood stations in Gansu, which had a great impact on laboratory testing capacity and subsequent development. It is suggested that governments at all levels and health administrative departments optimize the input of laboratory resource allocation according to the blood collection volume of blood stations to gradually narrow the differences in resource distribution between different regions, improve the degree of laboratory automation and optimize the personnel structure, so as to build high-quality and efficient blood testing laboratories and ensure the safety of clinical blood use.

Abstract Immune checkpoint inhibitors (ICIs) targeting CTLA-4 and PD-1/PD-L1 to boost tumor-specific T lymphocyte immunity have opened up new avenues for the treatment of various histological types of malignancies, with the possibility of durable responses and improved survival. However, the development of acquired resistance to ICI therapy over time after an initial response remains a major obstacle in cancer therapeutics. The potential mechanisms of acquired resistance to ICI therapy are still ambiguous. In this review, we focused on the current understanding of the mechanisms of acquired resistance to ICIs, including the lack of neoantigens and effective antigen presentation, mutations of IFN‐γ/JAK signaling, and activation of alternate inhibitory immune checkpoints, immunosuppressive tumor microenvironment, epigenetic modification, and dysbiosis of the gut microbiome. Further, based on these mechanisms, potential therapeutic strategies to reverse the resistance to ICIs, which could provide clinical benefits to cancer patients, are also briefly discussed.

Leiomyosarcoma occurring in the bone as primary tumor localization is extremely scarce with limited cases described in the literature, accounting for less than 0.7% of all primary bone malignancies. Once distant metastasis occurs, patients have limited treatments and often a somber prognosis, which underscore the need for innovative and effective treatment approaches. The emerging evidence suggests that anti-angiogenic therapy could inhibit angiogenesis and normalize vascular permeability in the tumor microenvironment, which, in turn, would increase immune effector cell infiltration into tumors. Immunotherapy depends on the accumulation and activity of immune effector cells within the tumor microenvironment, and immune responses and vascular normalization seem to be reciprocally regulated. Immunotherapy combined with anti-angiogenic therapy has recently made great progress in the treatment of various types of tumors. However, the effectiveness of the combination treatment in metastatic leiomyosarcoma is undetermined. In this study, we presented a rare case of primary leiomyosarcoma of the bone located in the trochanteric region of the femur, accompanied by multiple distant metastases. After the failure of multi-line therapies including AI regiments as the adjuvant chemotherapy, anlotinib as the first-line therapy, GT regiment as the second-line therapy, and eribulin as the third-line therapy, the patient received combinational therapy with penpulimab plus lenvatinib. The best efficacy for this regimen was a partial response, with a progression-free survival of 8.4 months according to the iRECIST criteria. After a dissociated response was detected without severe toxicities, the patient received local radiotherapy and continued treatment on penpulimab plus lenvatinib and eventually achieved long-term survival benefits with a total of over 60 months of overall survival with good quality of life and ongoing treatment. As our previous retrospective study found that one-third of advanced STS patients could still achieve clinical benefits from rechallenge with multi-targeted tyrosine kinase inhibitors (TKIs), after the failure of previous TKI therapy, this case provided the potential clinical activity of immunotherapy combined with anti-angiogenic TKI rechallenge in metastatic leiomyosarcoma.

Adjacent closely spaced intersections with characteristics of short link distance and high pedestrian flow are primarily located in high-density urban areas. To address the problems of queue overflow, poor traffic operation, and high pedestrian travel delays, a pedestrian-motor vehicle signal optimization method for adjacent closely spaced intersections was proposed in this paper. First, the traffic flow entering the closely spaced intersections is divided into nonarterial and arterial flow categories to establish a delay model of pedestrian crossing. Then, a pedestrian crossing delay model based on pedestrian demand is constructed according to pedestrian crossing time and a space diagram. An optimization model for pedestrians and vehicles at adjacent closely spaced intersections is established, and an artificial intelligence algorithm is used to optimize this model. Finally, a selected case intersection is optimized. The results show that compared with a traditional single optimization method, vehicle delay decreased about 4%, 13.8%, 17.1%, and 25.9% and total pedestrian delay decreased by 3%, 15%, 25%, and 31%, respectively, for the four proposed scenarios.

Bus rapid transit (BRT) as a valid means of public transportation for overpopulated country of China is an especial mode of travel to relieve traffic congestion. Despite utilizing exclusive bus line, BRT constantly experiences delay at intersections when encountering a red signal. Transit signal priority (TSP) considered as a promising control strategy to improve the operation efficiency of BRT has been widely used at isolated intersections or arterials to reduce travel delay. However, as a transport with schedule, the unexpected arrival time of transit vehicle at stop lines of consecutive intersections inevitably affects the operation reliability of the BRT system. To solve the problem, this study develops an optimization model of conditional TSP for bus rapid transit with the objective of improving the on-time performance of the BRT system while mitigating adverse impacts on private vehicles. A stop-to-stop segment is established with both road sections and intersections for the consideration of the transit operation reliability. The constraints on the degree of saturation and queue overflow were considered for mitigating adverse impacts of TSP. A mixed-integer non-linear programming procedure is adopted to formulate the optimization model. The mathematical model is linearized and solved by the branch-and-bound method. Extensive numerical analyses are conducted, and the proposed conditional TSP strategy is compared with unconditional TSP and no-TSP control to evaluate its performance under various traffic and signal conditions. A case study of a BRT line in Shanghai, China, was selected to illustrate the effectiveness of the proposed model. For the tested scenarios, the transit on-time performance was improved by 21%, with an incurred cost of 3.4% increase in the delay of private vehicles. This indicates that the proposed model performs well in maintaining the reliability of the transit system with the least impact on general traffic.

BackgroundTertiary lymphoid structures (TLSs) have been proven to be predictive biomarkers of favorable clinical outcomes and response to immunotherapies in several solid malignancies. Nevertheless, the effect of TLSs in patients with breast cancer (BC) remains controversial. The objective of the current study is to investigate the clinicopathological and prognostic significance of TLSs in BC. Given the unique difficulties for detecting and quantifying TLSs, a TLS-associated gene signature based on The Cancer Genome Atlas (TCGA) BC cohort was used to validate and supplement our results.MethodsElectronic platforms (PubMed, Web of Science, EMBASE, the Cochrane Library, CNKI, and Wanfang) were searched systematically to identify relevant studies as of January 11, 2022. We calculated combined odds ratios (ORs) with 95% confidence intervals (CIs) to determine the relationship between clinicopathological parameters and TLSs. The pooled hazard ratios (HRs) and 95% CIs were also calculated to evaluate the prognostic significance of TLSs. The TLS signature based on the TCGA BC cohort was applied to validate and supplement our results.ResultsFifteen studies with 3,898 patients were eligible for enrollment in our study. The combined analysis indicated that the presence of TLSs was related to improved disease-free survival (DFS) (HR = 0.61, 95% CI: 0.41–0.90, p < 0.05) and overall survival (OS) (HR = 1.66, 95% CI: 1.26–2.20, p < 0.001). Additionally, the presence of TLSs was positively correlated with early tumor TNM stage and high tumor-infiltrating lymphocytes. TLS presence was positively related to human epidermal growth factor receptor 2 (HER-2) and Ki-67 but inversely correlated with the status of estrogen and progesterone receptor. Simultaneously, our study found that tumor immune microenvironment was more favorable in the high-TLS signature group than in the low-TLS signature group. Consistently, BC patients in the high-TLS signature group exhibited better survival outcomes compared to those in the low-TLS signature group, suggesting that TLSs might be favorable prognostic biomarkers.ConclusionsTLS presence provides new insight into the clinicopathological features and prognosis of patients with BC, whereas the factors discussed limited the evidence quality of this study. We look forward to consistent methods to define and characterize TLSs, and more high-quality prospective clinical trials designed to validate the value of TLSs alone or in combination with other markers.

The arrival time of bus at the stop is critical data in design of bus operational strategies. Especially for real-time control strategies (i.e., signal priority system), bus arrival time is usually predicted to assess the next bus operation condition in the future (i.e., bus bunching and reliability of transit service) and then can be used as a decision basis of current control actions. The signalized intersection and surrounding traffic are the key factors in bus travel time prediction, but most previous approaches focus on the impact of signal control on bus delay only. This paper proposes a prediction model for arrival time at bus stop under the influence of both upstream signalized intersection and surrounding traffic flow. Considering the affected range of signalized intersection and the dynamic variation of bus speed, bus running processes are evaluated separately (including processes from a given detection point to stop line, through intersection, and from intersection to bus stop). In the proposed models, bus speed is deduced according to the change of traffic density at different locations to reflect the micro-impact of surrounding traffic flow on bus operation. The observed bus travel time is collected from actual investigations at two bus stops incorporating signalized intersection in Jinan City and compared with the predicted travel time in the proposed model. The results show that the proposed model has a low mean relative error. In addition, through the analysis of the maximum relative error, it also can be seen that vehicle queuing with random arrival of vehicles at stop line makes a gap between the prediction and the actual situation, which will be the focus of further research.

As an undesired behavior of the transport system, headway fluctuation or even bus bunching reduce reliability of bus stop service for waiting passengers. This paper proposes a pre-control method to improve the balance of service intervals at downstream stop through an adjustment of green time for bus passing, in which priority and delay of bus passing can be achieved. The proposed pre-control strategies at intersection are triggered based on prediction of service intervals at downstream stop to select priority or delay strategy that includes adjusting starting and ending time of green light. Meanwhile, the influence of adjustment of green time on surrounding traffic delay of vehicle is also considered. The traffic delay is estimated for vehicles arriving during phases within associated two signal cycles induced by the signal adjustment. To derive optimal adjustment of green time, a multi-objective function is established and the objectives include deviation of the bus service intervals and traffic average delay. An exhaustive search algorithm is programmed to solve the objective function. The effects of control strategies are tested by numerical experiments based upon a real bus route in Changchun. Results show that the bus service reliability can be improved through a proper signal pre-control and, compared with the single control strategy with only bus delay, the standard deviations of service intervals with the average running time and the stochastic running time are improved by 8.53% and 7.31%, respectively.

Purpose: This study aimed to investigate the efficacy of cyclophotocoagulation with an illuminated laser probe under a noncontact wide-angle retinoscope in treating refractory glaucoma. Methods: Eleven patients (11 eyes) with refractory neovascular glaucoma were treated with ciliary body photocoagulation. Preoperative and postoperative corrected visual acuity, intraocular pressure (IOP), ophthalmofundoscopy, B-ultrasound and ultrasound biomicroscopy, optical coherence tomography, and fundus fluorescein angiography were performed. Results: Preoperative IOP ranged from 45 to 58 mmHg (mean 51.9 mmHg). At postoperative 1, 3, and 6 months, the IOPs ranged between 16 and 33 mmHg (mean 27.1 mmHg), 14–28 mmHg (mean 20.6 mmHg), and 14–28 mmHg (mean 18.5 mmHg), respectively. IOP at the last follow-up (range 7–12 months) was 15–24 mmHg (mean 18.8 mmHg). An average of 63.8% decrease in postoperative IOP was found in these patients with no associated complications. The postoperative fibrotic exudate, anterior chamber hyphema, and exudative choroidal detachment were all well-managed and resolved. No patients experienced intraocular lens deviation or dislocation, hypotonia oculi, atrophy of eyeball, retinal detachment, endophthalmitis, or sympathetic ophthalmia. Conclusion: Cyclophotocoagulation with an illuminated laser probe under a noncontact wide-angle retinoscope is a safe and effective technique for the treatment of neovascular glaucoma.

On-board data of detected vehicles play a critical role in the management of urban road traffic operation and the estimation of traffic status. Unfortunately, due to limitations of technology and privacy issues, the sampling frequency of the detected vehicle data is low and the coverage is also limited. Continuous vehicle trajectories cannot be obtained. To overcome the above problems, this paper proposes an unscented Kalman filter (UKF)-based method to reconstruct the trajectories at signalized intersections using sparse probe data of vehicles. We first divide the intersection into multiple road sections and use a quadratic programming problem to estimate the travel time of each section. The weight of each initial possible trajectory is calculated separately, and the trajectory is updated using the unscented Kalman filter (UKF); then, the trajectory between two updates is also obtained accordingly. Finally, the method is applied to the actual scenario provided by the NGSIM data and compared with the real trajectory. The mean absolute error (MAE) is adopted to evaluate the accuracy of the proposed trajectory reconstruction. Sensitivity analysis is provided in order to provide the requirement of sampling frequency to obtain highly accurate reconstructed vehicle trajectories under this method. The results demonstrate the applicability of the technique to the signalized intersection. Therefore, the method enables us to obtain richer and more accurate trajectory data information, providing a strong prior basis for future urban road traffic management and scholars using trajectory data for various studies.

The vehicle-pedestrian encounter at midblock crosswalks in urban centers is inevitable but the challenge to urban transportation planners is in achieving a balance between traffic flow efficiency and pedestrian safety. Vehicles are expected to yield to pedestrians who have a right of way at the midblock unsignalized crosswalks but, failure to yield causes conflicts that at times are fatal. This study investigated the effect of macroscopic factors on the vehicle yielding. Six environmental factors are considered: temporal gap size, number of traffic lanes, number of waiting pedestrians, position of pedestrian (whether on street kerb or median), traffic flow direction and presence (or absence) of monitoring ePolice. Video Data on six observed variables that influenced vehicle yielding was collected from 13 uncontrolled crosswalk locations in Shanghai city in the Peoples Republic of China. A Logit model with a 95.9% accuracy was developed to describe the vehicle yielding behavior. The results showed that gap size and number of traffic lanes had the highest influence on driver yielding decision and that drivers were more likely to yield if ePolice was present. The sensitivity analysis was conducted and appropriate recommendations on improving the pedestrians crossing safety were proposed accordingly.

Transit priority is a useful way of improving transit operations in urban networks. However, the through and left-turn buses are rarely prioritized simultaneously at isolated intersections in the existing studies. This paper presents a variable bus approach lane design with a bus guidance and priority control model, which can reduce the delay of both the through and left-turn buses. The variable bus approach lanes can be dynamically used for the through and left-turn buses during the various periods of a signal cycle by the integrated design of geometric layouts and signal timing. A detailed bus guidance and priority control optimization model is formulated to guide the buses entering the appropriate bus approach lanes, and it provides optimal signal priorities for buses. The effectiveness of the proposed method is validated by a case study and numerical experiments. The results show that, on average, the total passenger delay can be reduced by 5% for every 30 veh/h and 40 veh/h increase in the volume of through buses and left-turn buses, respectively. Moreover, a comparison between the proposed method and the conventional transit priority method reveals that significant improvements can be made in reducing delays using the proposed method even at intersections with high degree of the saturation.

BackgroundDengue fever is the most rapidly spreading mosquito-borne viral disease over the past 50 years, with a 30-fold increase in global incidence. Dengue vector control is a key component for the dengue control strategy, since no absolutely effective vaccine or drug is available yet. However, the rapid rise and spread of mosquito insecticide resistance have become major threats to the efficiency of insecticide-based vector control activities. Thus, innovative vector control tools are badly needed. This study aims to confirm the antivirus effectiveness of ivermectin on dengue virus type 2 (DENV-2) in Aedes albopictus (Skuse, 1894), then to explore its potential use in the combating to the dengue epidemics.MethodsAedes albopictus were first infected with DENV-2 in human whole blood, and at the fourth day after infectious blood feeding, they were divided into eight groups. Seven of them were held for six days with access to 0, 2, 4, 8, 16, 32 and 64 ng/ml ivermectin, respectively, and the last one was set as a historical control group, which was stored at -80°C until being detected at the same time with the other groups. Each mosquito was detected using real-time fluorescent RT-PCR kit. DENV-2 RNA concentration (copies/ml) and infection rate in each group were compared.ResultsBoth of quantitatively and qualitatively inhibiting effects of ivermectin have been detected in this study. Generally, DENV-2 replicated well in Aedes albopictus without ivermectin intervention, whose virus loads exhibited significantly higher when the mosquitoes were holding from 4 days to 10 days after infectious blood feeding. In contrast, with the treatment of ivermectin, the infection rate was reduced by as much as 49.63%. The regression equation between infection rates (Y2) and ivermectin concentration log2 values (X2) was obtained as Y2 = 91.41-7.21*X2 with R2 = 0.89.ConclusionIvermectin can directly or indirectly inhibit DENV-2 multiplication in Aedes albopictus. Moreover, the actual concentration for application in zooprophylaxis needs to be confirmed in the further field trials.

Transit signal priority is a useful way to improve transit operations in urban networks. Most of the existing studies have been conducted in conditions with low saturation to avoid the detrimental effects of vehicles without priority. However, from the public transit point of view, it is more meaningful to assign transit signal priority when the degree of the saturation intersections is high. This study proposes a signal control model for transit signal priority to minimize the overall delay at near-saturated intersection. The delay increment is calculated in three scenarios for buses and private vehicles according to the dissipation time of the vehicular queue. A set of constrains are set up to avoid queue overflows and to ensure the rationalization of the signal timing. The proposed control model is tested based on a case study and numerical experiments. The results show that the proposed model can reduce the total person delay at near-saturated intersections. The length of priority time, degree of saturation, and number of lanes are the three main influencing factors. More than 6% reductions in person delay can be obtained for undersaturated intersections when the priority time is less than 5 s. Moreover, even when the intersection saturation is 0.95, the bus signal priority can be applied if only the priority time is less than 5 s.

The dynamic lane assignment at signalized intersections is a possible countermeasure to address the traffic demand variability problem. However, the operational efficiency is affected by the unfamiliarity of the drivers. This paper evaluates the operational efficiency of the intersections with dynamic lane assignment using field data collected at five intersections in China. A total of 63488 vehicles were captured, which were divided into four groups according to the lanes they drive on: Group 1, the variable approach lane; group 2, the lane adjacent to the variable lane with the same lane-use; group 3, the lane adjacent to the variable lane with different lane-use of the variable lane; and group 4, the lanes with the same lane-use as the variable lane at other approaches of the intersection. The statistical analysis was conducted to identify the difference of saturation flow rate among the four groups. A saturation flow rate adjustment model was established accordingly. Results indicate that the using of the dynamic lane assignment decreases the saturation flow rate of the variable lane and the adjacent lane with different lane-use 22.86% and 9.80%, respectively. For the variable lane, the reduction of the saturation flow rate comes from three aspects: the unequal distribution of traffic (8.9%), the mandatory lane-changing (10.7%), and the lane blockage (4.9%).