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Abstract Multi-constraint UAV path planning problems can be viewed as many-objective optimization problems that can be solved by meta-heuristic algorithms with good self-organizing optimization capabilities. However, such algorithms mostly use random initializing methods, resulting in low-quality initial paths that reduce the efficiency of subsequent algorithmic searches. Moreover, as the number of objective functions increases, meta-heuristic algorithms face inadequate selection pressure and convergence capability, which lead to poor solution. In order to address these issues, this paper proposes a UAV path planning method based on the framework of multi-objective jellyfish search algorithm (UMOJS). Firstly, an initializing strategy based on Rapidly-exploring Random Trees (RRT) is proposed to achieve higher quality initial paths. Secondly, a jellyfish updating strategy guided by the class-optimal individual is designed to enhance the convergence ability of the algorithm. Furthermore, a set of predefined reference points is imported to obtain Pareto optimal solutions with better convergence and distribution in many-objective optimization problems. To evaluate the superiority of the proposed UMOJS algorithm, three different difficulties of simulated flight environments are constructed to verify its performance. The experimental results show that UMOJS is not only able to gain more UAV paths with shorter length, but also more evenly distributed Pareto optimal solutions compared to five meta-heuristic algorithms when the constraint conditions are satisfied.

Abstract Objective We aim to explore the differences of the psychological distress of postoperative chemotherapy patients with colorectal cancer between mindfulness intervention combined with homogeneous medical concepts and mindfulness intervention only. Methods One hundred patients with colorectal cancer undergoing chemotherapy after surgery from Sep 2020 to Sep 2022 were enrolled and divided into active control group (Solution centered nursing interventions; homogenized medical and nursing professional teams; dedicated personnel responsible for “admission notices”; Regular follow-up after discharge) and mindfulness group (homogeneous medical concept + and concentrated solution + Mindfulness intervention) with 50 cases in each group according to different nursing methods. Results After nursing, the physical function, emotional function, cognitive function, and social function of the patients in the mindfulness group were significantly higher than those in the active control group. However, the overall life and economic difficulties of the patients in the mindfulness group were significantly lower than those in the active control group (P

Objectives: To explore whether COVID-19 vaccination protects against hospital admission by preventing infections and severe disease. Methods: We leveraged the UK Biobank and studied associations of COVID-19 vaccination (BioNTech-BNT162b2 or Oxford-AstraZeneca-ChAdOx1) with hospitalizations from cardiovascular and other selected diseases (N = 393,544; median follow-up = 54 days among vaccinated individuals). Multivariable Cox, Poisson regression, propensity score matching, and inverse probability treatment weighting analyses were performed. We also performed adjustment using prescription-time distribution matching, and prior event rate ratio. Results: We observed that COVID-19 vaccination (at least one dose), compared with no vaccination, was associated with reduced short-term risks of hospitalizations from stroke (hazard ratio [HR] = 0.178, 95% confidence interval [CI]: 0.127-0.250, P = 1.50e-23), venous thromboembolism (HR = 0.426, CI: 0.270-0.673, P = 2.51e-4), dementia (HR = 0.114, CI: 0.060-0.216; P = 2.24e-11), non-COVID-19 pneumonia (HR = 0.108, CI: 0.080-0.145; P = 2.20e-49), coronary artery disease (HR = 0.563, CI: 0.416-0.762; P = 2.05e-4), chronic obstructive pulmonary disease (HR = 0.212, CI: 0.126-0.357; P = 4.92e-9), type 2 diabetes (HR = 0.216, CI: 0.096-0.486, P = 2.12e-4), heart failure (HR = 0.174, CI: 0.118-0.256, P = 1.34e-18), and renal failure (HR = 0.415, CI: 0.255-0.677, P = 4.19e-4), based on standard Cox regression models. Among the previously mentioned results, reduced hospitalizations for stroke, heart failure, non-COVID-19 pneumonia, and dementia were consistently observed across regression, propensity score matching/inverse probability treatment weighting, prescription-time distribution matching, and prior event rate ratio. The results for two-dose vaccination were similar. Conclusions: Taken together, this study provides further support to the safety and benefits of COVID-19 vaccination, and such benefits may extend beyond reduction of infection risk or severity per se. However, causal relationship cannot be concluded and further studies are required.

Wuchereria bancrofti is a parasite transmitted by mosquitoes and can cause a neglected tropical disease called Lymphatic filariasis. However, the genome of W. bancrofti was not well studied, making novel drug development difficult. This study aims to identify microRNA, annotate protein function, and explore the pathogenic mechanism of W. bancrofti by genome-wide analysis. Novel miRNAs were identified by analysis of expressed sequence tags (ESTs) from this parasite. Protein homology was obtained by a bidirectional best-hit strategy using BLAST. By an EST-based method, we identified 20 novel miRNAs in the genome. The AU content of these miRNAs ranged from 39.7% to 80.0%, with a mean of 52.9%. Among them, 14 miRNA homologs were present in mammal genomes, while six miRNA homologs were present in non-mammal genomes. By conducting a detailed sequence alignment using BLAST, we have successfully annotated the functions of 75 previously unannotated proteins, enhancing our understanding of the proteome and potentially revealing new targets for therapy. Homology distribution analysis indicated that a set of critical proteins were present in parasites and mosquitoes, but not present in mammals. By searching the literature, ten proteins were found to be involved in the pathogenic infection process of W. bancrofti. In addition, the miRNA–gene network analysis indicated that two pathogenic genes (CALR and HMGB2) are regulated by newly identified miRNAs. These genes were supposed to play key roles in the infection mechanism of W. bancrofti. In conclusion, our genome-wide analysis provided new clues for the prevention and treatment of W. bancrofti infection.

Objective: This study aimed to investigate the genomic alteration profiles of cervical cancer patients, examine the correlation between mutation patterns and clinical and immune attributes, and discover novel targets for treatment of individuals with cervical cancer. Methods: We performed targeted next-generation sequencing of tumor tissues and blood samples obtained from 45 cervical cancer patients to analyze somatic alterations, mutation patterns, and HLA alleles comprehensively. Additionally, we used flow cytometry to assess expression levels of immune checkpoint genes. Results: Notably, genes such as AR (78%), KMT2D (76%), and NOTCH1 (62%) exhibited higher mutation frequencies. Moreover, the tumor mutation burden (TMB) was significantly greater in HPV-positive cervical cancer patients than in HPV-negative patients (P=0.029). BMI (P=0.047) and mutations in BARD1 (P=0.034), CEP290 (P=4E-04), and SLX4 (P=0.0128) were identified as predictors of shorter overall survival in cervical cancer patients. Furthermore, the present study revealed significant upregulation of PD-1 (P=0.027) and Tim-3 (P=0.048) in the high mutant-allele tumor heterogeneity (MATH) cohort. In the elderly cervical cancer patient population, HLA-A03:01 emerged as a high-risk allele (OR=3.2, P

BackgroundThe combination of agonistic antibodies with immune checkpoint inhibitors presents a promising avenue for cancer immunotherapy. Our objective is to explore the co-expression of 4-1BB, ICOS, CD28, with PD-1 on CD8+ T cells in the peripheral blood and tumor tissue of cervical cancer(CC) patients, with a specific focus on the association between the co-expression levels of 4-1BB with PD-1 and clinical features, prognosis as well as immunotherapy response. The goal is to offer valuable insights into cervical cancer immunotherapy.MethodsIn this study, 50 treatment-naive patients diagnosed with CC were enrolled. Flow cytometry was used to detect PD-1/4-1BB, PD-1/ICOS and PD-1/CD28 co-expression on CD8+ T cells. Subsequent analysis aimed to investigate the differential co-expression between peripheral blood and cancer tissue, and also the correlation between co-expression and clinical features in these patients. Gene Expression Omnibus (GEO) datasets, The Cancer Genome Atlas (TCGA) cohort, The IMvigor210 cohort, The BMS038cohort and Immunophenoscores were utilized to investigate the correlation between PD-1/4-1BB and the immune microenvironment, prognosis, immunotherapy, and drug sensitivity in cervical cancer.ResultsThe co-expression levels of PD-1/4-1BB, PD-1/ICOS, and PD-1/CD28 on CD8+ tumor-infiltrating lymphocytes (TILs) were significantly higher in cervical cancer patients compared to those in peripheral blood. Clinical feature analysis reveals that on CD8+ TILs, the co-expression of PD-1/4-1BB is more closely correlated with clinical characteristics compared to PD-1/ICOS, PD-1/CD28, PD-1, and 4-1BB. Pseudo-time analysis and cell communication profiling reveal close associations between the subgroups harboring 4-1BB and PD-1. The prognosis, tumor mutation burden, immune landscape, and immunotherapy response exhibit statistically significant variations between the high and low co-expression groups of PD-1/4-1BB. The high co-expression group of PD-1/4-1BB is more likely to benefit from immunotherapy.ConclusionPD-1/4-1BB, PD-1/ICOS, and PD-1/CD28 exhibit elevated co-expression on CD8+TILs of cervical cancer, while demonstrating lower expression in circulating T cells. The co-expression patterns of PD-1/4-1BB significantly contributed to the prediction of immune cell infiltration characteristics, prognosis, and tailored immunotherapy tactics. PD-1/4-1BB exhibits potential as a target for combination immunotherapy in cervical cancer.

Abstract Objective We aimed to investigate the relationship between the expression of killer cell lectin like receptor G1 (KLRG1) in peripheral blood lymphocytes, and the clinical characteristics and prognosis in patients with locally advanced nasopharyngeal carcinoma (NPC), and to dynamically evaluate the changes of KLRG1 expression after treatment. Methods A total of 82 patients with locally advanced NPC and 44 healthy individuals were recruited in this study. The expression of KLRG1 on T, natural killer, and natural killer T cells in peripheral blood mononuclear cells (PBMCs) was detected by flow cytometry. Its relationship with clinical characteristics and prognosis of patients, as well as changes in KLRG1 expression in PBMCs after treatment, were investigated. Results The expression of KLRG1 in CD8+ T cells in PBMCs of NPC patients was 46.50 (29.10, 69.80)%, significantly higher than 32.50 (17.38, 61.00) % in healthy controls (Z = −2.290, p = 0.022). The expression of KLRG1 in CD3+ CD56+ natural killer T cells in PBMCs of patients was 29.50 (6.21, 78.00) %, significantly higher than 1.47 (0.62, 8.88)% in healthy controls (Z = −5.371, p

The use of immune checkpoint inhibitors in malignant tumors improves patient outcomes. Because single-agent immune checkpoint blockade has a low objective response rate, it is meaningful to explore combined blockade of immune checkpoint receptors. We aimed to investigate the co-expression of TIM-3 with TIGIT or 2B4 on peripheral blood CD8+ T cells from patients with locally advanced nasopharyngeal carcinoma. The correlation between co-expression level and clinical characteristics and prognosis was studied to provide a basis for immunotherapy for nasopharyngeal carcinoma. Flow cytometry was used to detect TIM-3/TIGIT and TIM-3/2B4 co-expression on CD8+ T cells. The differences in co-expression between patients and healthy controls were analyzed. The correlation between co-expression of TIM-3/TIGIT or TIM-3/2B4 and the patient clinical characteristics and prognosis was examined. Also, the correlation between the TIM-3/TIGIT or 2B4 co-expression and other common inhibitory receptors was analyzed. We further validated our results using mRNA data from the Gene Expression Omnibus (GEO) database. TIM-3/TIGIT and TIM-3/2B4 co-expression was upregulated on peripheral blood CD8+ T cells from patients with nasopharyngeal carcinoma. They were both correlated with poor prognosis. There was a correlation between TIM-3/TIGIT co-expression and patient age and pathological stage, whereas TIM-3/2B4 co-expression correlated with age and sex. CD8+ T cells with elevated mRNA levels of TIM3/TIGIT and TIM3/2B4 also showed increased expression of multiple inhibitory receptors, indicating T cell exhaustion in locally advanced nasopharyngeal carcinoma. TIM-3/TIGIT or TIM-3/2B4 can be used as potential targets for combination immunotherapy in locally advanced nasopharyngeal carcinoma.

For patients with lung disease, dry powder inhalers (DPI) are profoundly beneficial. The current study introduces and develops a series of dry powder inhalers (DPIs). A capsule-based (size 0) active DPI was considered. The study aims to investigate whether swirling flow and outlet capillary diameter (dc_out) affect the percentage of emitted doses (ED) released from the capsule. Spiral vanes were added to the capillary inlet to produce a swirling flow. Computational fluid dynamics (CFD) was applied to simulate the problem. The results were compared with previous in vitro and numerical studies to validate the results. Based on the derived results, the small swirl parameter (SP) enhances the secondary flow and recirculation zone. It increases the central jet flow, which increases the ED value by about 5–20% compared to no-swirl flow. However, as the airflow rate increases, the recirculation zone enlarges, vorticities become dominant, and asymmetrical flow patterns emerge. Consequently, ED % drops significantly (more than 50%). As dc_out decreases, the vorticities around the outlet capillary become more potent, which is undesirable. Indeed, the emptying of the capsule does not happen ideally. The research provides a perspective on the device's design and DPI performance.

Polygenic Risk Scores (PRS) show promise for facilitating cancer risk stratification. Here, the authors performed a large genome-wide association study and develop a PRS for nasopharyngeal carcinoma, which could improve risk stratification and personalized screening.

Abstract Background T cell epitopes are polypeptide fragments presented to T cell receptors by MHC molecules encoded by human leukocyte antigen (HLA) genes after antigen-presenting cell processing, which is the basis for the study of antigen immune mechanism and multi-epitope vaccine. This study investigated T cell response to HPV16 E6 and E7 in patients with cervical squamous cell carcinoma (CSCC). Also, the HLA-A allele distribution was compared among patients and evaluated as a factor to predict prognosis in these patients. Materials and methods This study recruited a total of 76 patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IIB–IIIB CSCC. Mononuclear cells were isolated from the peripheral blood before any treatment and then enzyme-linked immunosorbent spot (ELISpot) assay was employed to measure the E6 and E7-specific T cell response. HLA‐A alleles were typed using Sanger sequencing‐based typing techniques with DNA extracted from the peripheral blood. The correlation between the T cell responses, HLA‐A allele distribution and patient prognosis were analysed using the Kaplan–Meier method, univariate and multivariate Cox proportional hazard models. Results The frequency of HPV E6-specific T cell responses in patients with pelvic lymph node metastasis was lower than that in patients without metastasis (P = 0.022). The 5-year overall survival (OS) rates of patients were 87.5% for those responding to multiple overlapping peptides, 72.7% for those responding to 1–2 overlapping peptides and 47.7% for non-responders (P = 0.032). Cox regression analysis indicated that the presence of HLA*A02:07 was independently associated with worse OS (hazard ratio [HR] 3.042; 95% confidence interval [CI] 1.348–6.862; P = 0.007), while concurrent chemoradiation therapy (CCRT) was independently associated with better OS (HR 0.475; 95% CI 0.232–0.975; P = 0.042). Conclusion The results of our study demonstrated that the level of HPV16 E6-specific T cell response and HLA*A02:07 were correlated with prognosis in patients with advanced CSCC.

Leaf inclination is one of the most important components of the ideal architecture, which effects yield gain. Leaf inclination was shown that is mainly regulated by brassinosteroid (BR) and auxin signaling. Here, we reveal a novel regulator of leaf inclination, auxin transporter OsPIN1b. Two CRISPR-Cas9 homozygous mutants, ospin1b-1 and ospin1b-2, with smaller leaf inclination compared to the wild-type, Nipponbare (WT/NIP), while overexpression lines, OE-OsPIN1b-1 and OE-OsPIN1b-2 have opposite phenotype. Further cell biological observation showed that in the adaxial region, OE-OsPIN1b-1 has significant bulge compared to WT/NIP and ospin1b-1, indicating that the increase in the adaxial cell division results in the enlarging of the leaf inclination in OE-OsPIN1b-1. The OsPIN1b was localized on the plasma membrane, and the free IAA contents in the lamina joint of ospin1b mutants were significantly increased while they were decreased in OE-OsPIN1b lines, suggesting that OsPIN1b might action an auxin transporter such as AtPIN1 to alter IAA content and leaf inclination. Furthermore, the OsPIN1b expression was induced by exogenous epibrassinolide (24-eBL) and IAA, and ospin1b mutants are insensitive to BR or IAA treatment, indicating that the effecting leaf inclination is regulated by OsPIN1b. This study contributes a new gene resource for molecular design breeding of rice architecture.

Despite the expansion of PD-1 checkpoint blockade to multiple types of cancer, whether the programmed cell death 1 (PD-1) expression status on CD8+ tumour infiltrating lymphocytes (TILs) could be a prognostic factor in cervical cancer is still unclear. In this study, we performed ex vivo phenotypic analysis of PD-1 expression on CD8+ TILs by flow cytometry from 47 treatment-naïve cervical cancer patients. With a median follow-up of 26.1 months (95% confidence interval [CI], 24-28.2 months), we then linked the quantitative cellular expression results to progression-free survival and overall survival. Based on the intensity of PD-1 expression, we further categorised the cervical cancer patients into PD-1high expressers (29.8%, 14/47) and PD-1low expressers (70.2%, 33/47). Multivariate analysis revealed that PD-1high expressers are correlated with early recurrence (HR, 5.91; 95% CI, 1.03-33.82; P= 0.046). Univariate analysis also demonstrated that PD-1high expressers are associated with poor overall survival in cervical cancer (HR, 5.365; 95% CI, 1.55-18.6; P=0.008). Moreover, our study also demonstrated that CD8+/CD4+ TIL ratio and HPV infection status are risk factors for early relapse and mortality in cervical cancer patients. In conclusion, this study confirms that PD-1 expression status is an independent prognostic factor for progression free survival in cervical cancer. These findings could be important in predicting the relapse of cervical cancer as a cellular diagnosis method and could be important knowledge for the selection of prospective PD-1 blockade candidates.

Auxin is the earliest discovered plant hormone, which plays important roles in each aspect of plant growth and development. There are two main pathways for auxin to be transported from the synthetic site (such as young leaves and terminal buds) to the active site. First, auxin is transported over long distances through phloem in an unfixed direction throughout the whole plant. Second, short-distance polar transport between cells requires the participation of auxin carriers, including unidirectional transport from stem tip to root and local unidirectional transport between tissues. Polar transport is critical to the establishment and maintenance of the auxin concentration gradient, which specifically regulates plant growth and development and responds to environmental changes. In this article, we reviewed the research progress of auxin transporters AUX1/LAX, PIN, and ABCB families, and some potential auxin transporters in rice growth and development, which provide information for the interpretation of biological functions of polar auxin transport families and lay a foundation for the genetic improvement of important agronomic traits in rice.

The images that are captured in sand storms often suffer from low contrast and serious color cast that are caused by sand dust, and these issues will have significant negative effects on the performance of an outdoor computer vision system. To address these problems, a method based on halo-reduced dark channel prior (DCP) dehazing for sand dust image enhancement is proposed in this paper. It includes three components in sequence: color correction in the LAB color space based on gray world theory, dust removal using a halo-reduced DCP dehazing method, and contrast stretching in the LAB color space using a Gamma function improved contrast limited adaptive histogram equalization (CLAHE), in which a guided filter is used to improve the artifacts of the histogram equalization. Experiments on a large number of real sand dust images demonstrate that the proposed method can well remove the overall yellowing tone and dust haze effect and obtain normal visual colors and a detailed clear image.

Abstract Background Cervical cancer is attributable to human papilloma virus (HPV) infection in the majority cases. E1, an HPV derived-protein, plays an important role in the initiation and development of cervical cancer. Our study aims to investigate the HPV E1-specific T cell response in patients with cervical squamous cell carcinoma (CSCC). Methods A total of 66 CSCC patients with FIGO stage IIB-IIIB and 60 healthy controls were enrolled. Enzyme-Linked ImmunoSpot (ELISPOT) assays was used to measure the HPV E1-specific T cell response in the peripheral blood of these patients before treatment. The patients were treated with chemotherapy and/or radiotherapy and followed up clinically for three years. The relationship between the T cell response, various clinical characteristics and the prognosis were studied with univariate analysis, multivariate analysis and survival curve analysis. Results The frequency of HPV E1-specific T cell response in peripheral blood of cervical cancer patients was 59.09%, with mean response intensity 24.56 SFC/106 PBMCs. The frequency and intensity of HPV E1-specific T cell response in patients were higher than healthy controls(p

Abstract Because there is no temporal information available, rain removal with a single image is more challenging than that with a video. In this paper, we present a weighted median guided filtering method for rain removal with a single image. It consists of two filtering operations. Firstly, a weighted median filter is convoluted with an input rainy image to obtain a coarse rain-free image; then, guided filter is employed to obtain a refined rain-free image, where the coarse rain-free image is used as a guided image and convoluted with the input rainy image via guided filter. Experimental results show that the proposed method generated comparable results to the state-of-the-art algorithms with low computation cost.

Background: Cancer patients often display dysfunctional antitumor T-cell responses. Because noteworthy benefits of immune checkpoint pathway blockade, such as programmed cell death protein 1 (PD-1) inhibitors, have been achieved in multiple advanced cancers, the next critical question is which mono-blockade or combinatorial blockade regimens may reinvigorate antitumor T-cell immunity in those cancer patients while limiting immune-related adverse effects.Method: This study recruited, in total, 172 primary cancer patients (131 were blood-tumor-matched patients) who were treatment-naïve prior to the surgeries or biopsies covering the eight most prevalent types of cancer. With access to fresh surgical samples, this study simultaneously investigated the ex vivo expression level of eight known immune checkpoint receptors [PD-1, cytotoxic T-lymphocyte antigen-4 [CTLA-4], T-cell immunoglobulin and mucin-domain containing-3 [Tim-3], 2B4, killer cell lectin like receptor G1 [KLRG-1], TIGIT, B- and T-lymphocyte attenuator [BTLA], and CD160] on tumor-infiltrating T cells (TILs) and paired circulating T cells in blood from a 131-patient cohort.Results: We found increased an expression of PD-1 and Tim-3 but a decreased expression of BTLA on TILs when compared with peripheral blood from multiple types of cancer. Moreover, our co-expression analysis of key immune checkpoint receptors delineates “shared” subsets as PD-1+Tim-3+TIGIT+2B4+KLRG-1–CTLA-4– and PD-1+TIGIT+2B4+Tim-3–KLRG-1–CTLA-4– from bulk CD8 TILs. Furthermore, we found that a higher frequency of advanced differentiation stage T cells (CD27–CCR7–CD45RA–) among the “shared” subset (PD-1+Tim-3+TIGIT+2B4+KLRG-1–CTLA-4–) in bulk CD8 TILs was associated with poorly differentiated cancer type in cervical cancer patients.Conclusions: To our knowledge, our study is the first comprehensive analysis of key immune checkpoint receptors on T cells in treatment-naïve, primary cancer patients from the eight most prevalent types of cancer. These findings might provide useful information for future design of mono-blockade/combinatorial blockades and/or genetically modified T-cell immunotherapy.

Objective: To investigate the effects of basic nursing combined with psychological intervention on treatment compliance, self-care ability, clinical efficacy, lung function and nursing satisfaction of patients with Influenza-A(H1N1). Method: This was application research. Eighty patients with influenza-A (H1N1) admitted to The First Affiliated Hospital of Hebei North University from January 2020 to December 2022 were included as subjects and randomly divided into the observation group(n=40) and the control group(n=40). Patients in the control group were given routine basic nursing intervention, while those in the observation group were treated with combined psychological intervention in addition to basic nursing. The differences in treatment compliance, self-care ability, clinical efficacy, lung function and nursing satisfaction were compared between the two groups. Results: After the intervention, the treatment compliance score and the total self-care ability score of the observation group were higher than those of the control group, with statistically significant differences(P<0.05). After treatment, the clinical efficacy of the observation group was significantly higher than that of the control group(P<0.05). Before treatment, no significant difference was observed between the two groups in terms of various indexes of lung function, which were better in the observation group than in the control group after treatment(P<0.05). Conclusion: Basic nursing combined with psychological intervention results in a variety of benefits in the treatment of patients with Influenza-A(H1N1), such as improved treatment compliance and self-care ability, ameliorated lung function, as well as enhanced treatment outcomes and nursing satisfaction, which needs to be promoted in clinical practice. [ABSTRACT FROM AUTHOR]