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Abstract Background The oncological outcomes of fertility-sparing surgery (FSS) compared to radical surgery (RS) in patients with stage I epithelial ovarian cancer (EOC) remain a subject of debate. We evaluated the risk ratios (RRs) for outcomes in patients with stage I EOC who underwent FSS versus RS. Methods We conducted a systematic search of PubMed, Web of Science, and Embase for articles published up to November 29, 2023. Studies that did not involve surgical procedures or included pregnant patients were excluded. We calculated the RRs for disease-free survival, overall survival, and recurrence rate. The quality of the included studies was assessed using the Cochrane Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool. The meta-analysis was registered on PROSPERO (CRD42024546460). Results From the 5,529 potentially relevant articles, we identified 83 articles for initial screening and included 12 articles in the final meta-analysis, encompassing 2,906 patients with epithelial ovarian cancer. There were no significant differences between the two groups in disease-free survival (RR [95% confidence interval {CI}], 0.90 [0.51, 1.58]; P = 0.71), overall survival (RR [95% CI], 0.74 [0.53, 1.03]; P = 0.07), and recurrence rate (RR [95% CI], 1.10 [0.69, 1.76]; P = 0.68). In sensitivity analyses, the significant difference was observed only for overall survival (before exclusion: RR [95% CI], 0.74 [0.53–1.03], P = 0.07; after exclusion: RR [95% CI], 0.70 [0.50–0.99]; P = 0.04). Conclusions This is the first and only individual patient data meta-analysis comparing disease-free survival, overall survival, and recurrence rate of patients with early-stage epithelial ovarian cancer undergoing FSS and RS. FSS was associated with similar disease-free survival and risk of recurrence as RS. We hypothesized that the decreased overall survival in the FSS group could not be attributed to distant metastases from epithelial ovarian cancer.

Abstract Platinum resistance represents a major barrier to the survival of patients with ovarian cancer (OC). Cdc2‐like kinase 2 (CLK2) is a major protein kinase associated with oncogenic phenotype and development in some solid tumors. However, the exact role and underlying mechanism of CLK2 in the progression of OC is currently unknown. Using microarray gene expression profiling and immunostaining on OC tissues, we found that CLK2 was upregulated in OC tissues and was associated with a short platinum‐free interval in patients. Functional assays showed that CLK2 protected OC cells from platinum‐induced apoptosis and allowed tumor xenografts to be more resistant to platinum. Mechanistically, CLK2 phosphorylated breast cancer gene 1 (BRCA1) at serine 1423 (Ser1423) to enhance DNA damage repair, resulting in platinum resistance in OC cells. Meanwhile, in OC cells treated with platinum, p38 stabilized CLK2 protein through phosphorylating at threonine 343 of CLK2. Consequently, the combination of CLK2 and poly ADP‐ribose polymerase inhibitors achieved synergistic lethal effect to overcome platinum resistance in patient‐derived xenografts, especially those with wild‐type BRCA1. These findings provide evidence for a potential strategy to overcome platinum resistance in OC patients by targeting CLK2.

Particle accelerators play a crucial role in scientific research, enabling the study of fundamental physics and materials science, as well as having important medical applications. This study proposes a novel graph learning approach to classify operational beamline configurations as good or bad. By considering the relationships among beamline elements, we transform data from components into a heterogeneous graph. We propose to learn from historical, unlabeled data via our self-supervised training strategy along with fine-tuning on a smaller, labeled dataset. Additionally, we extract a low-dimensional representation from each configuration that can be visualized in two dimensions. Leveraging our ability for classification, we map out regions of the low-dimensional latent space characterized by good and bad configurations, which in turn can provide valuable feedback to operators. This research demonstrates a paradigm shift in how complex, many-dimensional data from beamlines can be analyzed and leveraged for accelerator operations.

Abstract Background An immunosuppressive tumor microenvironment in ovarian cancer facilitates tumor progression and resistance to immunotherapy. The function of MYB Proto-Oncogene Like 2 (MYBL2) in the tumor microenvironment remains largely unexplored. Methods A syngeneic intraovarian mouse model, flow cytometry analysis, and immunohistochemistry were used to explore the biological function of MYBL2 in tumor progression and immune escape. Molecular and biochemical strategies—namely RNA-sequencing, western blotting, quantitative reverse transcription–polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay, multiplex immunofluorescence, chromatic immunoprecipitation assay (CHIP) and luciferase assay—were used to reveal the mechanisms of MYBL2 in the OVC microenvironment. Results We found tumor derived MYBL2 indicated poor prognosis and selectively correlated with tumor associated macrophages (TAMs) in ovarian cancer. Mechanically, C-C motif chemokine ligand 2 (CCL2) transcriptionally activated by MYBL2 induced TAMs recruitment and M2-like polarization in vitro. Using a syngeneic intraovarian mouse model, we identified MYBL2 promoted tumor malignancyand increased tumor-infiltrating immunosuppressive macrophages. Cyclin-dependent kinase 2 (CDK2) was a known upstream kinase to phosphorylate MYBL2 and promote its transcriptional function. The upstream inhibitor of CDK2, CVT-313, reprogrammed the tumor microenvironment and reduced anti-PD-1 resistance. Conclusions The MYBL2/CCL2 axis contributing to TAMs recruitment and M2-like polarization is crucial to immune evasion and anti-PD-1 resistance in ovarian cancer, which is a potential target to enhance the efficacy of immunotherapy.

Abstract Background Motor imagery brain-computer interfaces (BCIs) is a classic and potential BCI technology achieving brain computer integration. In motor imagery BCI, the operational frequency band of the EEG greatly affects the performance of motor imagery EEG recognition model. However, as most algorithms used a broad frequency band, the discrimination from multiple sub-bands were not fully utilized. Thus, using convolutional neural network (CNNs) to extract discriminative features from EEG signals of different frequency components is a promising method in multisubject EEG recognition. Methods This paper presents a novel overlapping filter bank CNN to incorporate discriminative information from multiple frequency components in multisubject motor imagery recognition. Specifically, two overlapping filter banks with fixed low-cut frequency or sliding low-cut frequency are employed to obtain multiple frequency component representations of EEG signals. Then, multiple CNN models are trained separately. Finally, the output probabilities of multiple CNN models are integrated to determine the predicted EEG label. Results Experiments were conducted based on four popular CNN backbone models and three public datasets. And the results showed that the overlapping filter bank CNN was efficient and universal in improving multisubject motor imagery BCI performance. Specifically, compared with the original backbone model, the proposed method can improve the average accuracy by 3.69 percentage points, F1 score by 0.04, and AUC by 0.03. In addition, the proposed method performed best among the comparison with the state-of-the-art methods. Conclusion The proposed overlapping filter bank CNN framework with fixed low-cut frequency is an efficient and universal method to improve the performance of multisubject motor imagery BCI.

ObjectiveThis study investigated the diagnostic performance of thrombin–antithrombin complex (TAT), plasmin–α2 plasmin inhibitor complex (PIC), tissue plasminogen activator–plasminogen activator inhibitor complex (t-PAIC), and thrombomodulin (TM) in predicting the progression of massive cerebral infarction to the malignant cerebral artery infarction.MethodA total of 71 patients with massive cerebral infarction confirmed by imaging examination were divided into malignant cerebral artery infarction group (MCAI) and non-malignant cerebral artery infarction group (NMCAI) based on whether they progressed to MCAI after admission. TAT, PIC, t-PAIC, and TM were measured immediately after admission. The predictive performance was analyzed by the receiver characteristic operating curve (ROC).ResultThe median plasma concentrations of TM, PIC, TAT, and t-PAIC in the MCAI patients at admission were 10.65 IU/mL, 1.17 μg/mL, 12.25 ng/mL, and 13.85 ng/mL, respectively, which were higher than those in the NMCAI patients (9.00 IU/mL, 1.07 μg/mL, 4.60 ng/mL, and 8.70 ng/mL), and the difference was statistically significant (p = 0.045, p = 0.035, p = 0.004, and p = 0.003). Elevated plasma t-PAIC concentration was shown to be an independent risk factor for progression of massive cerebral infarction to MCAI (OR = 1.131) by multivariate logistic regression analysis. ROC curve analysis showed that t-PAIC was the best predictor of MCAI (AUC = 74.7%), with a sensitivity of 75.0% and specificity of 75.9% when t-PAIC concentration was ≥12.4 ng/mL; TAT had the highest specificity in predicting MCAI, with a specificity of 90.7% when the TAT concentration was ≥13.5 ng/mL.ConclusionThe detection of PIC, TAT, t-PAIC, and TM is a comprehensive assessment of vascular endothelial damage and activation of the coagulation and fibrinolytic systems and has predictive value for poor prognosis in patients with MCAI. The widespread use of these tests will likely greatly improve the early diagnosis rate of MCAI.

Introduction: Platinum-based chemotherapy is the first-line treatment strategy for ovarian cancer patients. The dismal prognosis of ovarian cancer was shown to be stringently associated with the heterogeneity of tumor cells in response to this therapy, therefore understanding platinum sensitivity in ovarian cancer would be helpful for improving patients’ quality of life and clinical outcomes. HRDetect, utilized to characterize patients’ homologous recombination repair deficiency, was used to predict patients’ response to platinum-based chemotherapy. However, whether each of the single features contributing to HRD score is associated with platinum sensitivity remains elusive.Methods: We analyzed the whole-exome sequencing data of 196 patients who received platinum-based chemotherapy from the TCGA database. Genetic features were determined individually to see if they could indicate patients’ response to platinum-based chemotherapy and prognosis, then integrated into a Pt-score employing LASSO regression model to assess its predictive performance.Results and discussion: Multiple genetic features, including bi-allelic inactivation of BRCA1/2 genes and genes involved in HR pathway, multiple somatic mutations in genes involved in DNA damage repair (DDR), and previously reported HRD-related features, were found to be stringently associated with platinum sensitivity and improved prognosis. Higher contributions of mutational signature SBS39 or ID6 predicted improved overall survival. Besides, arm-level loss of heterozygosity (LOH) of either chr4p or chr5q predicted significantly better disease-free survival. Notably, some of these features were found independent of HRD. And SBS3, an HRD-related feature, was found irrelevant to platinum sensitivity. Integrated all candidate markers using the LASSO model to yield a Pt-score, which showed better predictive ability compared to HRDetect in determining platinum sensitivity and predicting patients’ prognosis, and this performance was validated in an independent cohort. The outcomes of our study will be instrumental in devising effective strategies for treating ovarian cancer with platinum-based chemotherapy.

ObjectiveThis study investigated the diagnostic performance of the thrombin-antithrombin complex (TAT), plasmin-α2 plasmin inhibitor complex (PIC), tissue plasminogen activator-plasminogen activator inhibitor complex (t-PAIC), and thrombomodulin (TM) in the early identification of massive cerebral infarction.MethodA total of 423 patients with cerebral infarction confirmed by imaging examination were divided into the massive cerebral infarction (MCI) group and the non-massive cerebral infarction (NMCI) group. TAT, PIC, t-PAIC, and TM were measured immediately after admission. The diagnostic performance was analyzed by the receiver characteristic operating curve (ROC).ResultThe median plasma concentrations of TAT, PIC, and t-PAIC in patients with MCI at early onset were 5.10 ng/ml, 1.11 μg/ml, and 8.80 ng/ml, respectively, which were higher than those in patients with NMCI (2.20 ng/ml, 0.59 μg/ml, and 7.35 ng/ml), and the difference was statistically significant (P < 0.001). TAT was shown to be an independent risk factor for the development of massive cerebral infarction by a multivariate logistic regression analysis (OR = 1.138). A ROC curve analysis showed that PIC had the best performance in identifying MCI at an early stage (AUC = 82.8%), with a sensitivity of 80.7% and a specificity of 76.2% when the PIC concentration was ≥0.8 μg/ml; TAT had the highest specificity in identifying MCI, with a specificity of 80.6% when the TAT concentration was ≥3.97 ng/ml.ConclusionThe detection of PIC, TAT, t-PAIC, and TM is a comprehensive assessment of vascular endothelial damage and activation of the coagulation and fibrinolytic systems and has diagnostic value for early identification of patients with MCI, which, together with its ease of detection, can be used as a plasma marker for early identification of large vessel occlusion.

Prevalent copy number alteration is the most prominent genetic characteristic associated with ovarian cancer (OV) development, but its role in immune evasion has not been fully elucidated. In this study, we identified RAD21, a key component of the cohesin complex, as a frequently amplified oncogene that could modulate immune response in OV. Through interrogating the RAD21-regulated transcriptional program, we found that RAD21 directly interacts with YAP/TEAD4 transcriptional corepressors and recruits the NuRD complex to suppress interferon (IFN) signaling. In multiple clinical cohorts, RAD21 overexpression is inversely correlated with IFN signature gene expression in OV. We further demonstrated in murine syngeneic tumor models that RAD21 ablation potentiated anti–PD-1 efficacy with increased intratumoral CD8+ T cell effector activity. Our study identifies a RAD21–YAP/TEAD4–NuRD corepressor complex in immune modulation, and thus provides a potential target and biomarker for precision immunotherapy in OV.

Eleven highly pathogenic avian influenza H5N8 viruses (clade 2.3.4.4b) were detected in migratory birds in Central China between November and December 2020, which were highly homologous to strains isolated in Europe from October to December 2020. Phylogenetic analysis indicated that the strains in the study possibly spread from Siberia by migratory birds. In this study, we found H5N8 virus infection in migratory birds could cause severe pathological damage and high viral load in multiple organs.

Abstract Background Vascular endothelial growth factor (VEGF)-targeted therapy is effective in patients with ovarian cancer. Whether adipose tissue (AT) could predict the efficacy of VEGF receptor (VEGFR) inhibitors in ovarian cancer is unknown. We aimed to evaluate the ability of distinct AT depots to predict the efficacy of apatinib, a VEGFR inhibitor, in recurrent ovarian cancers included in the AEROC trial. Methods The AEROC was a single-arm phase 2 trial of apatinib and oral etoposide in patients with platinum-resistant or platinum-refractory ovarian cancer. Apatinib was administered continuously, and oral etoposide was administered every 21 days for a maximum of six cycles. This was a post hoc study based on the AEROC trial. Areas of visceral AT (VAT), subcutaneous AT (SAT), and intermuscular AT (IMAT) were measured using computed tomography scan at baseline to assess their association with the objective response rate, progression-free survival, and overall survival. Results Of the 35 treated patients, 31 patients with at least one post-baseline efficacy assessment by computed tomography scan were included in this study. After adjusting for apatinib exposure, high VAT (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.03–0.90, P = 0.037) and SAT (OR, 0.16; 95% CI, 0.03–0.87, P = 0.034) were significantly associated with a higher objective response rate. Further, decreased risks of disease progression and death were associated with high VAT (hazard ratio [HR], 0.39; 95% CI, 0.17–0.92, P = 0.031, and HR, 0.12; 95% CI, 0.04–0.40, P

PurposeTreatment of epithelial ovarian cancer is evolving towards personalization and precision, which require patient-specific estimates of overall survival (OS) and progression-free survival (PFS).Patients and MethodsMedical records of 1173 patients who underwent debulking surgery in our center were comprehensively reviewed and randomly allocated into a derivation cohort of 879 patients and an internal validation cohort of 294 patients. Five hundred and seventy-seven patients from the other three cancer centers served as the external validation cohort. A novel nomogram model for PFS and OS was constructed based on independent predictors identified by multivariable Cox regression analysis. The predictive accuracy and discriminative ability of the model were measured using Harrell’s concordance index (C-index) and calibration curve.ResultsThe C-index values were 0.82 (95% CI: 0.76–0.88) and 0.84 (95% CI: 0.78–0.90) for the PFS and OS models, respectively, substantially higher than those obtained with the FIGO staging system and most nomograms reported for use in epithelial ovarian cancer. The nomogram score could clearly classify the patients into subgroups with different risks of recurrence or postoperative mortality. The online versions of our nomograms are available at https://eocnomogram.shinyapps.io/eocpfs/ and https://eocnomogram.shinyapps.io/eocos/.ConclusionA externally validated nomogram predicting OS and PFS in patients after R0 reduction surgery was established using a propensity score matching model. This nomogram may be useful in estimating individual recurrence risk and guiding personalized surveillance programs for patients after surgery, and it could potentially aid clinical decision-making or stratification for clinical trials.

In this project, we will explore the range of data-related decisions made during public health emergencies like the ongoing COVID-19 pandemic and analyze the flow of information, data, and metadata within networks of such decisions.Data sharing is now considered a key component of addressing present, future, and even past public health emergencies, from local to global levels. Researchers, research institutions, journals and others have taken steps towards increasing the sharing of data around the ongoing COVID-19 pandemic and in preparation for future pandemics.We will quantify the effects of data flow modifications to identify parameter sets under which specific modes of sharing or withholding information have the largest effects on outbreak dynamics. For these high-impact parameter sets, we will then assess the current and past availability of corresponding data, metadata, and misinformation, and estimate the effects on outbreak mitigation and preparedness efforts.

ObjectiveTo evaluate the value of routine preoperative gastroscopy/colonoscopy in patients with suspected ovarian cancer for differential diagnosis and judgment of bowel resection.MethodsAll women diagnosed with suspected ovarian cancer who underwent gastroscopy/colonoscopy before surgery in our center were retrospectively identified. Gastroscopy/colonoscopy results and clinical pathology, imaging, and surgical findings were analyzed.Results389 patients were included. Among them, 40 (including 13 gastric and 9 colonic malignancy) were ovarian metastasis. Compared with imaging, gastrointestinal endoscopy showed no statistical advantage in the specificity and sensitivity (99.4% vs. 99.7%, P=1.0; 55.0% vs. 45.2%, P=0.057; respectively). All patients with gastric/colonic cancer metastasize except for one had indicative imaging or tumor marker abnormalities. Three patients with colonic cancer metastases underwent optimal surgery and alive with no recurrence, the other 19 patients experienced palliative chemotherapy. There is no significant difference in the sensitivity of colonoscopy and imaging in predicting intestinal incision (61.5% vs. 43.8%, P=0.804), whereas the latter had higher specificity (87.8% vs. 74.3%, P=0.001).ConclusionsFor patients with suspected ovarian cancer, the incidence of gastrointestinal metastases is low, routine gastroscopy/colonoscopy before treatment is less efficient. Gastroscopy/colonoscopy has limited power to predict the need for gastrointestinal resection before ovarian cancer surgery.

Cytokine-induced killer (CIK) cells are demonstrated to possess potent cytolytic effect against ovarian cancer cells in vitro and in vivo. However, the clinical efficacy of maintenance therapy of CIK cells in patients with epithelial ovarian cancer (EOC) after first-line treatment remains unclear. This retrospective study included 646 cases of postoperative EOC patients, 72 of which received chemotherapy and sequential immunotherapy (CIT group), and 574 of which received only chemotherapy (Control group). Patients in the CIT group received at least four cycles of CIK cell (range 8.0 × 109 – 1.3 × 1010 cells) transfusion, with the interval of each cycle being 2 weeks. Survival analysis showed a significantly higher overall survival (OS) rate in the CIT group compared with the control group, as well as a favorable progression-free survival (PFS). Univariate and multivariate analyses indicated that adjuvant CIT was an independent prognostic factor for the OS of patients with EOC. Furthermore, subgroup analyses showed that adjuvant CIT significantly improved the OS of patients older than 45 years, with CA125 ≤ 1000, or with moderate or poorly differentiated tumors, and prolonged the PFS of patients with residual disease > 1 cm. Additionally, Kaplan-Meier analyses revealed that a higher fraction of CD3+CD8+/CD3+CD56+ phenotypes or lower percentage of CD3+CD4+/CD3−CD56+ phenotypes in the infused CIK cells significantly associated with better survival of patients with EOC. Furthermore, across all processes of CIK cell immunotherapy in the CIT group, 12.5% (9/72) of patients developed self-limiting light fevers and shivering at grade 1 or 2. No immunotherapy-related serious reactions were recorded. These data indicate that adjuvant CIT with CIK cells is an effective therapeutic approach to prolonging the survival of EOC patients.