Intelligent classification of cardiotocography based on a support vector machine and convolutional neural network: Multiscene research.

OBJECTIVE: To propose a computerized system utilizing multiscene analysis based on a support vector machine (SVM) and convolutional neural network (CNN) to assess cardiotocography (CTG) intelligently. METHODS: We retrospectively collected 2542 CTG records of singleton pregnancies delivered at the maternity ward of the First Affiliated Hospital of Xi'an Jiaotong University from October 10, 2020, to August 7, 2021. CTG records were divided into five categories (baseline, variability, acceleration, deceleration, and normality). Apart from the category of normality, the other four different categories of abnormal data correspond to four scenes. Each scene was divided into training and testing sets at 9:1 or 7:3. We used three computer algorithms (dynamic threshold, SVM, and CNN) to learn and optimize the system. Accuracy, sensitivity, and specificity were performed to evaluate performance. RESULTS: The global accuracy, sensitivity, and specificity of the system were 93.88%, 93.06%, and 94.33%, respectively. In acceleration and deceleration scenes, when the convolution kernel was 3, the test data set reached the highest performance. CONCLUSION: The multiscene research model using SVM and CNN is a potential effective tool to assist obstetricians in classifying CTG intelligently.

The sealing effect of magnetic-sealing uterine manipulator in isolated uterus from patients with early-stage cervical cancer: a pre-clinical study.

OBJECTIVE: Traditional uterine manipulator is considered as the main reason for short survival of patients with early-stage cervical cancer during minimally invasive surgery. This study aims to assess the sealing effect of magnetic-sealing uterine manipulators (MUMs) in isolated uteruses. METHODS: The study was performed on isolated uterus from patients with early-stage cervical cancer who underwent open abdominal radical hysterectomy between November 2019 to April 2021. Right-angle forceps closure tests (groups 1 and 3) were defined as control tests. One experimental MUM closure test (group 2) and 2 control tests were respectively carried out in each of the isolated uterus. DNA ploidy analysis system was used to observe exfoliated cells. Statistical analysis was performed using Wilcoxon signed-rank test to assess the sealing effect of MUM. RESULTS: We identified 36 patients. No regional node metastasis was discovered and only one tumor was larger than 4.0 cm in diameter. The mean of exfoliated tumor cells in groups 1, 2, and 3 were 1, 1, and 2, respectively. There was no significant difference in the quantity of exfoliated cells between groups 1 and 3 (p=0.476), so the results of the 2 groups were merged. Subsequently, a significant difference was observed between combined right-angle forceps closure tests and MUM closure tests (p=0.022). CONCLUSION: The sealing effect of MUM was better than that of right-angle forceps. MUM can effectively seal cervical cancer cells in the cup cover, avoiding the dissemination of tumor cells. TRIAL REGISTRATION: Chinese Clinical Trial Register Identifier: ChiCTR1900026012.

Application of Nanozymes in Environmental Monitoring, Management, and Protection.

Nanozymes are nanomaterials with enzyme-like activity, possessing the unique properties of nanomaterials and natural enzyme-like catalytic functions. Nanozymes are catalytically active, stable, tunable, recyclable, and versatile. Therefore, increasing attention has been paid in the fields of environmental science and life sciences. In this review, we focused on the most recent applications of nanozymes for environmental monitoring, environmental management, and environmental protection. We firstly introduce the tuning catalytic activity of nanozymes according to some crucial factors such as size and shape, composition and doping, and surface coating. Then, the application of nanozymes in environmental fields are introduced in detail. Nanozymes can not only be used to detect inorganic ions, molecules, organics, and foodborne pathogenic bacteria but are also involved in the degradation of phenolic compounds, dyes, and antibiotics. The capability of nanozymes was also reported for assisting air purification, constructing biofuel cells, and application in marine antibacterial fouling removal. Finally, the current challenges and future trends of nanozymes toward environmental fields are proposed and discussed.

Progress in the Development of Detection Strategies Based on Olfactory and Gustatory Biomimetic Biosensors.

The biomimetic olfactory and gustatory biosensing devices have broad applications in many fields, such as industry, security, and biomedicine. The development of these biosensors was inspired by the organization of biological olfactory and gustatory systems. In this review, we summarized the most recent advances in the development of detection strategies for chemical sensing based on olfactory and gustatory biomimetic biosensors. First, sensing mechanisms and principles of olfaction and gustation are briefly introduced. Then, different biomimetic sensing detection strategies are outlined based on different sensing devices functionalized with various molecular and cellular components originating from natural olfactory and gustatory systems. Thereafter, various biomimetic olfactory and gustatory biosensors are introduced in detail by classifying and summarizing the detection strategies based on different sensing devices. Finally, the future directions and challenges of biomimetic biosensing development are proposed and discussed.

A Computer-Aided Diagnosis System of Fetal Nucleated Red Blood Cells With Convolutional Neural Network.

CONTEXT.­: The rapid recognition of fetal nucleated red blood cells (fNRBCs) presents considerable challenges. OBJECTIVE.­: To establish a computer-aided diagnosis system for rapid recognition of fNRBCs by convolutional neural network. DESIGN.­: We adopted density gradient centrifugation and magnetic-activated cell sorting to extract fNRBCs from umbilical cord blood samples. The cell-block method was used to embed fNRBCs for routine formalin-fixed paraffin sectioning and hematoxylin-eosin staining. Then, we proposed a convolutional neural network-based, computer-aided diagnosis system to automatically discriminate features and recognize fNRBCs. Extracting methods of interested region were used to automatically segment individual cells in cell slices. The discriminant information from cellular-level regions of interest was encoded into a feature vector. Pathologic diagnoses were also provided by the network. RESULTS.­: In total, 4760 pictures of fNRBCs from 260 cell-slides of 4 umbilical cord blood samples were collected. On the premise of 100% accuracy in the training set (3720 pictures), the sensitivity, specificity, and accuracy of cellular intelligent recognition were 96.5%, 100%, and 98.5%, respectively, in the test set (1040 pictures). CONCLUSIONS.­: We established a computer-aided diagnosis system for effective and accurate fNRBC recognition based on a convolutional neural network.

Characterization and Functional Prediction of Bacteria in Ovarian Tissues.

The theory of a "sterile" female upper reproductive tract has been encountering increasing opposition due to advancements in bacterial detection. However, whether ovaries contain bacteria has not yet been confirmed yet. Herein, an experiment to detect bacteria in ovarian tissues was introduced. We chose ovarian cancer patients in the cancer group and noncancerous patients in the control group. 16S rRNA gene sequencing was used to differentiate bacteria in ovarian tissues from the cancer and control groups. Furthermore, we predicted the functional composition of the identified bacteria by using BugBase and PICRUSt. This method can also be used in other viscera and tissues since many organs have been proven to harbor bacteria in recent years. The presence of bacteria in viscera and tissues may help scientists evaluate cancerous and normal tissues and may be aid in the treatment of cancer.

Near-Infrared Fluorescent Agent for In Vitro Screening of Endometrial Cancer and Precancerous Lesions.

The lack of cytopathologists delays the advancement of screening for endometrial cancer. It was urgent to develop a new dye for rapid diagnosis. Our study aimed to synthesize a targeted folate receptor-α near-infrared (NIR) fluorescent agent, folic acid-zwitterionic NIR fluorophore (ZW-FA), and explore the feasibility for screening of endometrial cancer and precancerous change. Folic acid was conjugated with zwitterionic NIR fluorophore. The preparation of ZW-FA was validated by 1H NMR, mass spectrometric, ultraviolet spectra and fluorescence spectra. ZW-FA was incubated with endometrial cytology samples obtained from patients who underwent dilation and curettage or total hysterectomy. Diagnostic utility was calculated by applying laser confocal microscope, Image-J and statistical models, such as enumeration, receiver operating characteristic curve, logistic regression, support vector machine and decision tree were used. The purity of ZW-FA was > 95% determined by 1H NMR. ZW-FA had the strongest absorption peak at 633 nm in ultraviolet spectra. Photostability of ZW-FA was over 8 hours. In clinical validation, a total of 92 patients were enrolled. The cut-off value of ZW-FA was 49 in enumeration, which was used to distinguish the type of samples. Indicators about diagnostic utility are as follows: sensitivity 90.77%, specificity 62.96%, false-positive rate 37.04%, false-negative rate 9.23%, positive predictive value 85.51% and negative predictive value 73.91%. The samples processed by ZW-FA did not affect further Hematoxylin-Eosin staining and pathological diagnosis. It was an effective cytologic strategy for in vitro diagnosis of endometrial cancer and precancerous change by using ZW-FA. CLINICAL TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx, identifier ChiCTR1800020123.

A polygenic methylation prediction model associated with response to chemotherapy in epithelial ovarian cancer.

To identify potential aberrantly differentially methylated genes (DMGs) correlated with chemotherapy response (CR) and establish a polygenic methylation prediction model of CR in epithelial ovarian cancer (EOC), we accessed 177 (47 chemo-sensitive and 130 chemo-resistant) samples corresponding to three DNA-methylation microarray datasets from the Gene Expression Omnibus and 306 (290 chemo-sensitive and 16 chemo-resistant) samples from The Cancer Genome Atlas (TCGA) database. DMGs associated with chemotherapy sensitivity and chemotherapy resistance were identified by several packages of R software. Pathway enrichment and protein-protein interaction (PPI) network analyses were constructed by Metascape software. The key genes containing mRNA expressions associated with methylation levels were validated from the expression dataset by the GEO2R platform. The determination of the prognostic significance of key genes was performed by the Kaplan-Meier plotter database. The key genes-based polygenic methylation prediction model was established by binary logistic regression. Among accessed 483 samples, 457 (182 hypermethylated and 275 hypomethylated) DMGs correlated with chemo resistance. Twenty-nine hub genes were identified and further validated. Three genes, anterior gradient 2 (AGR2), heat shock-related 70-kDa protein 2 (HSPA2), and acetyltransferase 2 (ACAT2), showed a significantly negative correlation between their methylation levels and mRNA expressions, which also corresponded to prognostic significance. A polygenic methylation prediction model (0.5253 cutoff value) was established and validated with 0.659 sensitivity and 0.911 specificity.

Clinical Evaluation of Li Brush Endometrial Samplers for Diagnosing Endometrial Lesions in Women With Intrauterine Devices.

Background: For women with intrauterine devices (IUDs), it is difficult to sample the endometrium when abnormal uterine bleeding occurs or when regular screening of endometrial cancer is proposed. The purpose of this study is to evaluate the validity of endometrial sampling using Li Brush in IUD users. Methods: This study was a prospective cohort study and conducted in two parts. Part I was to assess the impact of Li Brush on the position of IUDs. Transvaginal ultrasound was used to locate IUDs before and after sampling. Part II was to explore the diagnostic accuracy of Li Brush in detecting endometrial lesions. IUD users with irregular uterine bleeding were recruited in the IUD group and IUD non-users who arranged for dilatation and curettage (D&C) were recruited in the control group. The endometrium was sampled by Li Brush for cells and by D&C for tissues in both groups. The satisfactoriness of sampling and validity of Li Brush were evaluated. Results: Seventeen cases in part I confirmed no significant difference in the position of IUDs before and after sampling (p = 0.20). 112 IUD users and 139 IUD non-users were recruited in part II. Li Brush achieved 94.64 and 92.09% satisfactory sampling rates in the IUD group and control group, respectively, without statistically significant difference between the two groups (p = 0.42). The Sensitivity and specificity of Li Brush for detection of endometrial lesions in IUD group were 95.35 and 87.76% respectively. Conclusions: Li Brush used for endometrial biopsy did not affect the position of IUDs and had high yield of satisfactory samples and good validity for endometrial diagnoses. It was feasible to screen endometrial lesions by Li Brush for women with IUDs.

Research on the Multiagent Joint Proximal Policy Optimization Algorithm Controlling Cooperative Fixed-Wing UAV Obstacle Avoidance.

Multiple unmanned aerial vehicle (UAV) collaboration has great potential. To increase the intelligence and environmental adaptability of multi-UAV control, we study the application of deep reinforcement learning algorithms in the field of multi-UAV cooperative control. Aiming at the problem of a non-stationary environment caused by the change of learning agent strategy in reinforcement learning in a multi-agent environment, the paper presents an improved multiagent reinforcement learning algorithm-the multiagent joint proximal policy optimization (MAJPPO) algorithm with the centralized learning and decentralized execution. This algorithm uses the moving window averaging method to make each agent obtain a centralized state value function, so that the agents can achieve better collaboration. The improved algorithm enhances the collaboration and increases the sum of reward values obtained by the multiagent system. To evaluate the performance of the algorithm, we use the MAJPPO algorithm to complete the task of multi-UAV formation and the crossing of multiple-obstacle environments. To simplify the control complexity of the UAV, we use the six-degree of freedom and 12-state equations of the dynamics model of the UAV with an attitude control loop. The experimental results show that the MAJPPO algorithm has better performance and better environmental adaptability.

Two-Pronged Treatment of Hemoperitoneum and Abnormal Uterine Bleeding in an Adolescent Girl With Congenital Fibrinogen Deficiency.

Introduction: If a woman suffers from congenital fibrinogen deficiency (CFD), she might undergo hypermenorrhea monthly and possibly to suffer from hemoperitoneum due to a ruptured follicle or corpus luteal cyst every month, which seriously threaten her health and quality of life. Here, we creatively used a combination of the levonorgestrel-releasing intrauterine system (LNG-IUS) and the combined oral contraceptives (COC) for a girl with CFD. Case presentation: A 14-year-old girl presented with no obvious cause of persistent and severe lower abdominal pain that began 8 h prior. After examination, she was diagnosed as hemoperitoneum. CFD was diagnosed when she was 2 years old and she had two hospitalizations due to hemorrhagic anemia caused by menorrhagia. Therefore, after successful conservative treatment of hemoperitoneum, a combination of LNG-IUS and COC was used for the long-term conservative management of hypermenorrhea and hemoperitoneum. During the half-year of follow-up, she had hypomenorrhea without hemoperitoneum. Conclusions: To the best of our knowledge, this was the first patient treated with such a procedure in the literature, and we recommend every woman with CFD at puberty or reproductive age receives this two-pronged treatment.

The differential distribution of bacteria between cancerous and noncancerous ovarian tissues in situ.

BACKGROUND: With the improvement of bacterial detection, the theory of the sterile female upper reproductive tract has been frequently challenged in recent years. However, thus far, no researchers have used ovaries as study targets. METHODS: Six women who were diagnosed with ovarian cancer were included in the cancer group, and ten women who were diagnosed with a noncancerous ovarian condition (including three patients with uterine myoma and seven patients with uterine adenomyosis) were included in the control group. Immunohistochemistry staining using an antibacterial lipopolysaccharide (LPS) antibody was used to confirm the presence of bacteria in the ovarian tissues. In addition, 16S rRNA sequencing was used to compare the differences in the bacteria between ovarian cancer tissues and noncancerous ovarian tissues. BugBase and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) were used to predict the functional composition of the bacteria. RESULTS: Bacterial LPS was present in ovarian cancer tissue and noncancerous ovarian tissue, which implied the presence of bacteria in ovarian tissue. When compared to the noncancerous ovarian bacteria at the phylum level, the cancerous ovarian bacteria were composed of increased Aquificae and Planctomycetes and decreased Crenarchaeota. When predicting metagenomes, gene functions associated with the potentially pathogenic and the oxidative stress-tolerant phenotype were enriched in the ovaries of the cancer group. Forty-six significantly different KEGG pathways existed in the ovarian bacteria of the cancer group compared to that of the control group. CONCLUSIONS: Different bacteria compositions were present in cancerous and noncancerous ovarian tissues. TRIAL REGISTRATION: Chines Clinical Trail Registry, CHiCTR1800020018, Registered 11 September 2018, http://www.chictr.org.cn/.

Selective estrogen receptor modulator with estrogen does not affect the proliferation and apoptosis of uterine leiomyoma cells.

BACKGROUND: The administration of menopausal hormone therapy (MHT) in women with uterine leiomyomas is still debated. The purpose of this article is to study the proliferation and apoptosis of uterine leiomyoma cells under the impact of selective estrogen receptor modulator (SERM) combined with estrogen. METHODS: Primary cultured uterine leiomyoma cells in the perimenopausal period were treated with estrogen (17-beta estradiol) + SERM (raloxifene) as the tissue selective estrogen complex (TSEC) group, while both estrogen + medroxyprogesterone acetate (E+P) and estrogen (E) alone as were used as control groups. The expression of proliferating cell nuclear antigen (PCNA) and B-cell lymphoma-2 (Bcl-2) proteins was assessed by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and western-blot analysis, respectively. RESULTS: The proliferation in the TSEC group was weaker than the control groups (P<0.001). There was no statistical difference between the TSEC and blank control group on cell proliferation at 72 h (P=0.13). However, there was a significant difference between the other groups (P<0.001). PCNA expression of TSEC was lower than that of the E + P and E groups (P<0.05). There was no statistical difference in the expression of PCNA between the TSEC and blank control groups (P=0.63). Bcl-2 expression of TSEC was lower than that of the E + P and E groups (P<0.05). There was no statistical difference in the expression of Bcl-2 between the TSEC group and the blank control group (P=0.60). CONCLUSIONS: SERM combined with estrogen may have a better safety for perimenopausal women with uterine leiomyoma in MHT.

The Discordance of Gene Mutations between Circulating Tumor Cells and Primary/Metastatic Tumor.

Circulating tumor cells (CTCs) are an important part in the field of "liquid biopsy." However, major questions remain to be answered whether the mutations in the CTCs represent the mutations in primary tumor tissue and metastatic tumors. We compared the genetic mutations between CTCs and their matched tumors, and extracted data on the heterogeneity of the mutational status in CTCs and the change in mutations of CTCs before and during treatment. For mutations detected in single genes, we calculated the concordance of the mutations between the CTCs and primary tumor tissue. For mutations detected in multiple genes, we calculated the concordance of the mutations between the CTCs and primary/metastatic tumor tissue. The heterogeneity of the mutational status is clearly present in CTCs. For mutations detected in a single gene, the overall concordance of mutations is 53.05%. For mutations detected in multiple genes, the concordance of mutations is extremely different. The heterogeneity of the mutational status existed in single CTCs, and the mutational status of CTCs was discordant with that of tumor tissue.