PTPRO-related CD8⁺ T-cell signatures predict prognosis and immunotherapy response in patients with breast cancer

Background: Poor immunogenicity and extensive immunosuppressive T-cell infiltration in the tumor immune microenvironment (TIME) have been identified as potential barriers to immunotherapy success in “immune-cold” breast cancers. Thus, it is crucial to identify biomarkers that can predict immunotherapy efficacy. Protein tyrosine phosphatase receptor type O (PTPRO) regulates multiple kinases and pathways and has been implied to play a regulatory role in immune cell infiltration in various cancers. Methods: ESTIMATE and single-sample gene set enrichment analysis (ssGSEA) were performed to uncover the TIME landscape. The correlation analysis of PTPRO and immune infiltration was performed to characterize the immune features of PTPRO. Univariate and multivariate Cox analyses were applied to determine the prognostic value of various variables and construct the PTPRO-related CD8+ T-cell signatures (PTSs). The Kaplan–Meier curve and the receiver operating characteristic (ROC) curve were used to estimate the performance of PTS in assessing prognosis and immunotherapy response in multiple validation datasets. Results: High PTPRO expression was related to high infiltration levels of CD8+ T cells, as well as macrophages, activated dendritic cells (aDCs), tumor-infiltrating lymphocytes (TILs), and Th1 cells. Given the critical role of CD8+ T cells in the TIME, we focused on the impact of PTPRO expression on CD8+ T-cell infiltration. The prognostic PTS was then constructed using the TCGA training dataset. Further analysis showed that the PTS exhibited favorable prognostic performance in multiple validation datasets. Of note, the PTS could accurately predict the response to immune checkpoint inhibitors (ICIs). Conclusion: PTPRO significantly impacts CD8+ T-cell infiltration in breast cancer, suggesting a potential role of immunomodulation. PTPRO-based PTS provides a new immune cell paradigm for prognosis, which is valuable for immunotherapy decisions in cancer patients

A compact ka-band active integrated antenna with a GaAs amplifier in a ceramic package

This letter presents the design of a Ka-band active integrated antenna in package (AIAiP). A monolithic microwave integrated circuit amplifier based on the GaAs process and a compact patch antenna based on the printed circuit board process are implemented, respectively. Then, the amplifier and antenna are assembled together in a specified package using the wire-bond process. Thus, compared to the traditional solutions, the transmission loss and the size of the proposed AIAiP are significantly reduced. Furthermore, the influence of the bonding wire and the package is taken into account in the design of the amplifier and the antenna, respectively. A good agreement between the simulation and measurement results can be observed. The proposed AIAiP occupies a compact size of 7 × 7 mm2. Meanwhile, it achieves -10-dB impedance bandwidth from 33.4 to 37.2 GHz and a peak gain of 18.9 dBi at 35 GHz. Additionally, the impact of the package size on the antenna performance has been demonstrated for future AIA designers

A bibliometric and visualization analysis on the association between chronic exposure to fine particulate matter and cancer risk

Introduction:As one of the major pollutants in ambient air pollution, fine particulate matter (PM2.5) has attracted public attention. A large body of laboratory and epidemiological research has shown that PM2.5 exposure is harmful to human health.MethodsTo investigate its association with the commonly observed PM-related cancer, a bibliometric study was performed on related publications from 2012 to 2021 from a macroscopic perspective with the help of the Web of Science database and scientometric software VOSviewer, CiteSpace V, HistCite, and Biblioshiny.ResultsThe results indicated that of the 1,948 enrolled documents, scientific productions increased steadily and peaked in 2020 with 348 publications. The most prolific authors, journals, organizations, and countries were Raaschou-Nielsen O, Science of the Total Environment, the Chinese Academy of Sciences, and China, respectively. The top five keywords in frequency order were “air pollution,” “particulate matter,” “lung cancer,” “exposure,” and “mortality.”DiscussionThe toxic mechanism of carcinogenicity was explained and is worthy of further investigation. China and the US collaborated most closely, and it is hoped the two countries can strengthen their collaboration to combat air pollution. There is also a need to identify the components of PM2.5 and refine the models to assess the global burden of disease attributed to PM2.5 exposure

Raman spectroscopy characterization of structural evolution in middle-rank coals

The second coalification jump which occurred during the middle-rank led to abrupt changes of many physical and chemical properties of coal, and the change of the aggregate structure may be the fundamental reason. In order to investigate the structural evolution characteristics of middle-rank coal and its relation with the second coalification jump in detail, the structure characteristics of six middle-rank coals (Ro,max=1.10%−1.63%) that across the second coalification jump were studied by Raman spectroscopy, and the structural parameters were calculated by fitting the first-order and second-order Raman spectrum using the fitting software. The results indicated that the evolution of Raman structural parameters with Ro,max is not linear, reflecting the complexity of the structural evolution of coal. According to the evolution characteristics of Raman structural parameters, the coalification during the stage of Ro,max=1.10%−1.63% can be divided into three stages. The turning points are located near Ro,max=1.30% and Ro,max=1.50%, respectively, which are exactly equivalent to the positions of the second and the third coalification jump discovered in previous research. It indicated that the Raman structural parameters can reflect the occurrence of the coalification jump, moreover, Raman spectroscopy is an effective method to study the coal structure. The first stage is Ro,max=1.10%−1.30%, the long-chain aliphatic structures cracked and the remained shorter-chain aliphatic hydrocarbons and aliphatic substituted structures on the aromatic rings will form new alicyclic structures, which caused the branched degree increases and hindered the alignment of aromatic systems in coal. The order degree of aromatic system is thus reached the least near Ro,max=1.30%, with the smallest WG, the largest FG/D, the smallest AD/AG, the increase of AS/A1, and the significant decrease of A(2G)R/A2. In the second stage of Ro,max=1.30%−1.50%, the aromatization of the alicyclic structures formed in the previous stage resulted in an increase in the content of aromatic C—H structure and the least of amorphous carbon structure. Besides, the degree of aromatization and aromatic structural both increased, which showed that A(GR+VL+VR)/AD, A(GR+VL+VR)/AG and FG/D decreased significantly, AD/AG increased, WG and d(G-D) increased quickly. The last stage is Ro,max=1.50%−1.63%, the condensation reaction occurred between the aromatic rings formed in the second stage, leading to the reduction of A(2G)R/A2. Meanwhile, the various bridging bonds between aromatic ring systems continued to break, resulting in the formation of some small-scale aromatic structures, as evidenced by a decrease in A(2G)R/A2, a small decrease in WG, and an increase in A(GR+VL+VR)/AD and A(GR+VL+VR)/AG. These results are the basis for deeply understanding the mechanism of coalification jump and coalification

Tumor-Derived Exosomal Protein Tyrosine Phosphatase Receptor Type O Polarizes Macrophage to Suppress Breast Tumor Cell Invasion and Migration

Tumor-derived exosomes, containing multiple nucleic acids and proteins, have been implicated to participate in the interaction between tumor cells and microenvironment. However, the functional involvement of phosphatases in tumor-derived exosomes is not fully understood. We and others previously demonstrated that protein tyrosine phosphatase receptor type O (PTPRO) acts as a tumor suppressor in multiple cancer types. In addition, its role in tumor immune microenvironment remains elusive. Bioinformatical analyses revealed that PTPRO was closely associated with immune infiltration, and positively correlated to M1-like macrophages, but negatively correlated to M2-like macrophages in breast cancer tissues. Co-cultured with PTPRO-overexpressing breast cancer cells increased the proportion of M1-like tumor-associated macrophages (TAMs) while decreased that of M2-like TAMs. Further, we observed that tumor-derived exosomal PTPRO induced M1-like macrophage polarization, and regulated the corresponding functional phenotypes. Moreover, tumor cell-derived exosomal PTPRO inhibited breast cancer cell invasion and migration, and inactivated STAT signaling in macrophages. Our data suggested that exosomal PTPRO inhibited breast cancer invasion and migration by modulating macrophage polarization. Anti-tumoral effect of exosomal PTPRO was mediated by inactivating STAT family in macrophages. These findings highlight a novel mechanism of tumor invasion regulated by tumor-derived exosomal tyrosine phosphatase, which is of translational potential for the therapeutic strategy against breast cancer

A scientometric analysis of research trends on targeting mTOR in breast cancer from 2012 to 2022

Over the past decade, thousands of articles have been published on the mechanistic target of rapamycin (mTOR) and its role in breast cancer. However, the variability and heterogeneity of academic data may impact the acquisition of published research information. Due to the large number, heterogeneity, and varying quality of publications related to mTOR and breast cancer, sorting out the present state of the research in this area is critical for both researchers and clinicians. Therefore, scientometric techniques and visualization tools were employed to analyze the large number of bibliographic metadata related to the research area of mTOR and breast cancer. The features of relevant publications were searched from 2012 to 2022 to evaluate the present status of research and the evolution of research hotspots in this particular field. Web of Science was utilized to extract all relevant publications from 2012 to 2022. Subsequently, Biblioshiny and VOSviewer were utilized to obtain data on the most productive countries, authors, and institutions, annual publications and citations, the most influential journals and articles, and the most frequently occurring keywords. In total, 1,471 publications were retrieved, comprising 1,167 original articles and 304 reviews. There was a significant rise in publications between 2015 and 2018, followed by a sharp decline in 2019 and a rebound since then. The publication with the highest number of citations was a 2012 review authored by Baselga et al. The United States had the highest number of publications, citations and connections among all countries. Oncotarget had the highest number of published articles among all the journals, and José Baselga had the strongest links with other authors. Excluding the search topics, the most frequently used words were “expression” (n = 297), “growth” (n = 228), “activation” (n = 223), “pathway” (n = 205), and “apoptosis” (n = 195). mTOR is crucially involved in breast cancer pathogenesis, but its exact mechanism of action remains controversial and warrants further investigation. The scientometric analysis provides a distinct overview of the existing state of research and highlights the topical issues that deserve further exploration

Dynamic Query Forms for Database Queries

Abstract-Modern scientific databases and web databases maintain large and heterogeneous data. These real-world databases contain over hundreds or even thousands of relations and attributes. Traditional predefined query forms are not able to satisfy various ad-hoc queries from users on those databases. This paper proposes DQF, a novel database query form interface, which is able to dynamically generate query forms. The essence of DQF is to capture a user's preference and rank query form components, assisting him/her to make decisions. The generation of a query form is an iterative process and is guided by the user. At each iteration, the system automatically generates ranking lists of form components and the user then adds the desired form components into the query form. The ranking of form components is based on the captured user preference. A user can also fill the query form and submit queries to view the query result at each iteration. In this way, a query form could be dynamically refined till the user satisfies with the query results. We utilize the expected F-measure for measuring the goodness of a query form. A probabilistic model is developed for estimating the goodness of a query form in DQF. Our experimental evaluation and user study demonstrate the effectiveness and efficiency of the system

Dynamic Query Forms for Database Queries

Abstract-Modern scientific databases and web databases maintain large and heterogeneous data. These real-world databases contain over hundreds or even thousands of relations and attributes. Traditional predefined query forms are not able to satisfy various ad-hoc queries from users on those databases. This paper proposes DQF, a novel database query form interface, which is able to dynamically generate query forms. The essence of DQF is to capture a user's preference and rank query form components, assisting him/her to make decisions. The generation of a query form is an iterative process and is guided by the user. At each iteration, the system automatically generates ranking lists of form components and the user then adds the desired form components into the query form. The ranking of form components is based on the captured user preference. A user can also fill the query form and submit queries to view the query result at each iteration. In this way, a query form could be dynamically refined till the user satisfies with the query results. We utilize the expected F-measure for measuring the goodness of a query form. A probabilistic model is developed for estimating the goodness of a query form in DQF. Our experimental evaluation and user study demonstrate the effectiveness and efficiency of the system

1 Dynamic Query Forms for Database Queries

Abstract—Modern scientific databases and web databases maintain large and heterogeneous data. These real-world databases contain over hundreds or even thousands of relations and attributes. Traditional predefined query forms are not able to satisfy various ad-hoc queries from users on those databases. This paper proposes DQF, a novel database query form interface, which is able to dynamically generate query forms. The essence of DQF is to capture a user’s preference and rank query form components, assisting him/her to make decisions. The generation of a query form is an iterative process and is guided by the user. At each iteration, the system automatically generates ranking lists of form components and the user then adds the desired form components into the query form. The ranking of form components is based on the captured user preference. A user can also fill the query form and submit queries to view the query result at each iteration. In this way, a query form could be dynamically refined till the user satisfies with the query results. We utilize the expected F-measure for measuring the goodness of a query form. A probabilistic model is developed for estimating the goodness of a query form in DQF. Our experimental evaluation and user study demonstrate the effectiveness and efficiency of the system

A Low Creatinine to Body Weight Ratio Predicts the Incident Nonalcoholic Fatty Liver Disease in Nonelderly Chinese without Obesity and Dyslipidemia: A Retrospective Study

Aim. A lower ratio of creatinine to body weight (Cr/BW) is considered the independent risk factor for incident nonalcoholic fatty liver disease (NAFLD). However, the relationship between the Cr/BW ratio and NAFLD among individuals without obesity and dyslipidemia and how this relationship is impacted by age are still ambiguous. Therefore, we explored the effect of the Cr/BW ratio on the incident NAFLD among Chinese without obesity and dyslipidemia of different age groups. Methods. A total of 9756 participants without NAFLD at baseline were included and grouped by the median value (1.32) of the Cr/BW ratio. Then, a further analysis was stratified by age (60 years old). The primary outcome was new-onset NAFLD. Results. After a median follow-up of 2.76 years, 844 (8.7%) participants developed NAFLD. The elderly had a higher person-years incidence rate and cumulative incidence rate than the nonelderly. A high Cr/BW ratio showed a lower cumulative incidence compared to a low Cr/BW ratio for the whole population (P=0.039) and the nonelderly group (P=0.008). After being adjusted for multivariate variables, the lower Cr/BW ratio was the independent risk factor for incident NAFLD in the nonelderly (HR 0.718, 95% CI 0.548-0.942), instead of the elderly. Conclusions. The Cr/BW ratio has a negative relationship with incident NAFLD among nonobese Chinese without dyslipidemia before the age of 60