Real-time conflict risk at signalized intersection using drone video: A random parameters logit model with heterogeneity in means and variances.

Signalized intersections are crash prone. This can be attributed to driver errors, red light running behaviour, and poor coordination of conflicting traffic. It is anticipated that overall crash risk at signalized intersection would increase when mixed traffic like motorcycles is involved. In this study, a real-time prediction model for motorcycle and non-motorcycle involved conflict risk at the signalized intersection is proposed. For example, high-resolution vehicle and motorcycle trajectory data are extracted from drone videos using advanced computer vision techniques. Additionally, conflict types including rear-end, angle, and head-on conflicts are also considered. Then, the multinomial logit approach is adopted to model the propensity of severe and slight vehicle-vehicle and vehicle-motorcycle conflicts. Furthermore, the problem of unobserved heterogeneity is addressed using the random parameters model with heterogeneity in means and variances. Results indicate that risk of vehicle-vehicle conflict is significantly associated with vehicle speed and acceleration, and conflict type, and that of vehicle-motorcycle conflict is associated with vehicle speed and acceleration, motorcycle lateral speed, conflict type, and time to green signal. Findings should shed light to the development and implementation of optimal traffic signal time plan and traffic management strategy that can mitigate the potential crash risk, especially involving motorcycles, at the signalized intersection.

Design and Proofreading of the English-Chinese Computer-Aided Translation System by the Neural Network.

At present, complete machine translation (MT) cannot meet the needs of information communication and cultural exchange, and the speed of complete human translation is too slow. Therefore, if MT is used to assist in the process of English-Chinese translation, it can not only prove that machine learning (ML) can translate English to Chinese but also improve the translation efficiency and accuracy of translators through human-machine cooperation. The research on the mutual cooperation between ML and human translation has an important research significance for translation systems. An English-Chinese computer-aided translation (CAT) system is designed and proofread based on a neural network (NN) model. First, it gives a brief overview of CAT. Second, the related theory of the NN model is discussed. An English-Chinese CAT and proofreading system based on the recurrent neural network (RNN) is constructed. Finally, the translation accuracy and proofreading recognition rate of the translation files of 17 different projects under different models are studied and analyzed. The research results reveal that according to the different translation properties of different texts, the average accuracy rate of text translation under the RNN model is 93.96%, and the mean accuracy of text translation under the transformer model is 90.60%. The translation accuracy of the RNN model in the CAT system is 3.36% higher than that of the transformer model. The English-Chinese CAT system based on the RNN model has different proofreading results for sentence processing, sentence alignment, and inconsistency detection of translation files of different projects. Among them, the recognition rate for sentence alignment and the inconsistency detection of English-Chinese translation is high, and the expected effect is achieved. The design of the English-Chinese CAT and proofreading system based on the RNN can make the translation and proofreading be carried out simultaneously, which greatly improves the efficiency of translation work. Meanwhile, the above research methods can improve the problems encountered in the current English-Chinese translation, provide a path for the bilingual translation process, and have certain promotion prospects.

Identification of biomarkers predictive of metastasis development in early-stage colorectal cancer using network-based regularization.

Colorectal cancer (CRC) is the third most common cancer and the second most deathly worldwide. It is a very heterogeneous disease that can develop via distinct pathways where metastasis is the primary cause of death. Therefore, it is crucial to understand the molecular mechanisms underlying metastasis. RNA-sequencing is an essential tool used for studying the transcriptional landscape. However, the high-dimensionality of gene expression data makes selecting novel metastatic biomarkers problematic. To distinguish early-stage CRC patients at risk of developing metastasis from those that are not, three types of binary classification approaches were used: (1) classification methods (decision trees, linear and radial kernel support vector machines, logistic regression, and random forest) using differentially expressed genes (DEGs) as input features; (2) regularized logistic regression based on the Elastic Net penalty and the proposed iTwiner-a network-based regularizer accounting for gene correlation information; and (3) classification methods based on the genes pre-selected using regularized logistic regression. Classifiers using the DEGs as features showed similar results, with random forest showing the highest accuracy. Using regularized logistic regression on the full dataset yielded no improvement in the methods' accuracy. Further classification using the pre-selected genes found by different penalty factors, instead of the DEGs, significantly improved the accuracy of the binary classifiers. Moreover, the use of network-based correlation information (iTwiner) for gene selection produced the best classification results and the identification of more stable and robust gene sets. Some are known to be tumor suppressor genes (OPCML-IT2), to be related to resistance to cancer therapies (RAC1P3), or to be involved in several cancer processes such as genome stability (XRCC6P2), tumor growth and metastasis (MIR602) and regulation of gene transcription (NME2P2). We show that the classification of CRC patients based on pre-selected features by regularized logistic regression is a valuable alternative to using DEGs, significantly increasing the models' predictive performance. Moreover, the use of correlation-based penalization for biomarker selection stands as a promising strategy for predicting patients' groups based on RNA-seq data.

Spatiotemporal evolution of the clear cell renal cell carcinoma microenvironment links intra-tumoral heterogeneity to immune escape.

BACKGROUND: Intratumoral heterogeneity (ITH) is a hallmark of clear cell renal cell carcinoma (ccRCC) that reflects the trajectory of evolution and influences clinical prognosis. Here, we seek to elucidate how ITH and tumor evolution during immune checkpoint inhibitor (ICI) treatment can lead to therapy resistance. METHODS: Here, we completed a single-arm pilot study to examine the safety and feasibility of neoadjuvant nivolumab in patients with localized RCC. Primary endpoints were safety and feasibility of neoadjuvant nivolumab. Then, we spatiotemporally profiled the genomic and immunophenotypic characteristics of 29 ccRCC patients, including pre- and post-therapy samples from 17 ICI-treated patients. Deep multi-regional whole-exome and transcriptome sequencing were performed on 29 patients at different time points before and after ICI therapy. T cell repertoire was also monitored from tissue and peripheral blood collected from a subset of patients to study T cell clonal expansion during ICI therapy. RESULTS: Angiogenesis, lymphocytic infiltration, and myeloid infiltration varied significantly across regions of the same patient, potentially confounding their utility as biomarkers of ICI response. Elevated ITH associated with a constellation of both genomic features (HLA LOH, CDKN2A/B loss) and microenvironmental features, including elevated myeloid expression, reduced peripheral T cell receptor (TCR) diversity, and putative neoantigen depletion. Hypothesizing that ITH may itself play a role in shaping ICI response, we derived a transcriptomic signature associated with neoantigen depletion that strongly associated with response to ICI and targeted therapy treatment in several independent clinical trial cohorts. CONCLUSIONS: These results argue that genetic and immune heterogeneity jointly co-evolve and influence response to ICI in ccRCC. Our findings have implications for future biomarker development for ICI response across ccRCC and other solid tumors and highlight important features of tumor evolution under ICI treatment. TRIAL REGISTRATION: The study was registered on ClinicalTrial.gov (NCT02595918) on November 4, 2015.

Comprehensive Genomic Profiling of Cell-Free Circulating Tumor DNA Detects Response to Ribociclib Plus Letrozole in a Patient with Metastatic Breast Cancer.

Analysis of cell-free circulating tumor DNA obtained by liquid biopsy is a non-invasive approach that may provide clinically actionable information when conventional tissue biopsy is inaccessible or infeasible. Here, we followed a patient with hormone receptor-positive and human epidermal growth factor receptor (HER) 2-negative breast cancer who developed bone metastases seven years after mastectomy. We analyzed circulating cell-free DNA (cfDNA) extracted from plasma using high-depth massively parallel sequencing targeting 468 cancer-associated genes, and we identified a clonal hotspot missense mutation in the PIK3CA gene (3:178952085, A > G, H1047R) and amplification of the CCND1 gene. Whole-exome sequencing revealed that both alterations were present in the primary tumor. After treatment with ribociclib plus letrozole, the genetic abnormalities were no longer detected in cfDNA. These results underscore the clinical utility of combining liquid biopsy and comprehensive genomic profiling to monitor treatment response in patients with metastasized breast cancer.

Genetic and microenvironmental intra-tumor heterogeneity impacts colorectal cancer evolution and metastatic development.

Colorectal cancer (CRC) is a highly diverse disease, where different genomic instability pathways shape genetic clonal diversity and tumor microenvironment. Although intra-tumor heterogeneity has been characterized in primary tumors, its origin and consequences in CRC outcome is not fully understood. Therefore, we assessed intra- and inter-tumor heterogeneity of a prospective cohort of 136 CRC samples. We demonstrate that CRC diversity is forged by asynchronous forms of molecular alterations, where mutational and chromosomal instability collectively boost CRC genetic and microenvironment intra-tumor heterogeneity. We were able to depict predictor signatures of cancer-related genes that can foresee heterogeneity levels across the different tumor consensus molecular subtypes (CMS) and primary tumor location. Finally, we show that high genetic and microenvironment heterogeneity are associated with lower metastatic potential, whereas late-emerging copy number variations favor metastasis development and polyclonal seeding. This study provides an exhaustive portrait of the interplay between genetic and microenvironment intra-tumor heterogeneity across CMS subtypes, depicting molecular events with predictive value of CRC progression and metastasis development.

Anisotropic terahertz transmission induced by the external magnetic field in La0.67Ca0.33MnO3 film.

A systemic investigation of the terahertz (THz) transmission of La0.67Ca0.33MnO3 film on the (001)-oriented NdGaO3 substrate under external magnetic field and low temperature have been performed. The significant THz absorption difference between the out-of-plane and the in-plane magnetic field direction is observed, which is consistent with the electrical transport measurement using the standard four-probe technique. Furthermore, we find that the complex THz conductivities can be reproduced in terms of the Drude Smith equation as the magnetic field is perpendicular to the film plane, whereas it deviates from this model when the in-plane magnetic field is applied. We suggest that such anisotropies in THz transport dynamics have close correspondences with the phase separation and anisotropic magnetoresistance effects in the perovskite-structured manganites. Our work demonstrates that the THz time-domain spectroscopy (TDS) can be an effective non-contact method for studying the magneto-transport properties of the perovskite-structured manganites.

Single-cell sequencing links multiregional immune landscapes and tissue-resident T cells in ccRCC to tumor topology and therapy efficacy.

Clear cell renal cell carcinomas (ccRCCs) are highly immune infiltrated, but the effect of immune heterogeneity on clinical outcome in ccRCC has not been fully characterized. Here we perform paired single-cell RNA (scRNA) and T cell receptor (TCR) sequencing of 167,283 cells from multiple tumor regions, lymph node, normal kidney, and peripheral blood of two immune checkpoint blockade (ICB)-naïve and four ICB-treated patients to map the ccRCC immune landscape. We detect extensive heterogeneity within and between patients, with enrichment of CD8A+ tissue-resident T cells in a patient responsive to ICB and tumor-associated macrophages (TAMs) in a resistant patient. A TCR trajectory framework suggests distinct T cell differentiation pathways between patients responding and resistant to ICB. Finally, scRNA-derived signatures of tissue-resident T cells and TAMs are associated with response to ICB and targeted therapies across multiple independent cohorts. Our study establishes a multimodal interrogation of the cellular programs underlying therapeutic efficacy in ccRCC.

HERVs establish a distinct molecular subtype in stage II/III colorectal cancer with poor outcome.

Colorectal cancer (CRC) is one of the most lethal malignancies. The extreme heterogeneity in survival rate is driving the need for new prognostic biomarkers. Human endogenous retroviruses (hERVs) have been suggested to influence tumor progression, oncogenesis and elicit an immune response. We examined multiple next-generation sequencing (NGS)-derived biomarkers in 114 CRC patients with paired whole-exome and whole-transcriptome sequencing (WES and WTS, respectively). First, we demonstrate that the median expression of hERVs can serve as a potential biomarker for prognosis, relapse, and resistance to chemotherapy in stage II and III CRC. We show that hERV expression and CD8+ tumor-infiltrating T-lymphocytes (TILs) synergistically stratify overall and relapse-free survival (OS and RFS): the median OS of the CD8-/hERV+ subgroup was 29.8 months compared with 37.5 months for other subgroups (HR = 4.4, log-rank P < 0.001). Combing NGS-based biomarkers (hERV/CD8 status) with clinicopathological factors provided a better prediction of patient survival compared to clinicopathological factors alone. Moreover, we explored the association between genomic and transcriptomic features of tumors with high hERV expression and establish this subtype as distinct from previously described consensus molecular subtypes of CRC. Overall, our results underscore a previously unknown role for hERVs in leading to a more aggressive subtype of CRC.

The interplay between cancer type, panel size and tumor mutational burden threshold in patient selection for cancer immunotherapy.

The tumor mutational burden (TMB) is increasingly recognized as an emerging biomarker that predicts improved outcomes or response to immune checkpoint inhibitors in cancer. A multitude of technical and biological factors make it difficult to compare TMB values across platforms, histologies, and treatments. Here, we present a mechanistic model that explains the association between panel size, histology, and TMB threshold with panel performance and survival outcome and demonstrate the limitations of existing methods utilized to harmonize TMB across platforms.