Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer.

BACKGROUND: The prospective phase III multi-centre L-MOCA trial (NCT03534453) has demonstrated the encouraging efficacy and manageable safety profile of olaparib maintenance therapy in the Asian (mainly Chinese) patients with platinum-sensitive relapsed ovarian cancer (PSROC). In this study, we report the preplanned exploratory biomarker analysis of the L-MOCA trial, which investigated the effects of homologous recombination deficiency (HRD) and programmed cell death ligand 1 (PD-L1) expression on olaparib efficacy. METHODS: HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan-Meier method was utilised to analyse progression-free survival (PFS). RESULTS: This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5-22.1) versus 9.2 months (95% CI: 7.5-13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4-18.2) versus 22.2 months (95% CI: 18.3-NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9-NA) versus 8.3 months (95% CI: 6.7-13.8)]. CONCLUSIONS: HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2. TRIAL REGISTRATION: NCT03534453. Registered at May 23, 2018.

Niraparib maintenance therapy using an individualised starting dose in patients with platinum-sensitive recurrent ovarian cancer (NORA): final overall survival analysis of a phase 3 randomised, placebo-controlled trial.

Background: Niraparib significantly prolonged progression-free survival versus placebo in patients with platinum-sensitive, recurrent ovarian cancer (PSROC), regardless of germline BRCA mutation (gBRCAm) status, in NORA. This analysis reports final data on overall survival (OS). Methods: This randomised, double-blind, placebo-controlled, phase 3 trial enrolled patients across 30 centres in China between 26 September 2017 and 2 February 2019 (clinicaltrials.gov, NCT03705156). Eligible patients had histologically confirmed, recurrent, (predominantly) high-grade serous epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma (no histological restrictions for those with gBRCAm) and had received ≥2 prior lines of platinum-based chemotherapy. Patients were randomised (2:1) to receive niraparib or placebo, with stratification by gBRCAm status, time to recurrence following penultimate platinum-based chemotherapy, and response to last platinum-based chemotherapy. Following a protocol amendment, the starting dose was individualised: 200 mg/day for patients with bodyweight <77 kg and/or platelet count <150 × 103/µL at baseline and 300 mg/day otherwise. OS was a secondary endpoint. Findings: Totally, 265 patients were randomised to receive niraparib (n = 177) or placebo (n = 88), and 249 (94.0%) received an individualised starting dose. As of 14 August 2023, median follow-up for OS was 57.9 months (IQR, 54.8-61.6). Median OS (95% CI) with niraparib versus placebo was 51.5 (41.4-58.9) versus 47.6 (33.3-not evaluable [NE]) months, with hazard ratio [HR] of 0.86 (95% CI, 0.60-1.23), in the overall population; 56.0 (36.1-NE) versus 47.6 (31.6-NE) months, with HR of 0.86 (95% CI, 0.46-1.58), in patients with gBRCAm; and 46.5 (41.0-NE) versus 46.9 (31.8-NE) months, with HR of 0.87 (95% CI, 0.56-1.35), in those without. No new safety signals were identified, and myelodysplastic syndromes/acute myeloid leukaemia occurred in three (1.7%) niraparib-treated patients. Interpretation: Niraparib maintenance therapy with an individualised starting dose demonstrated a favourable OS trend versus placebo in PSROC patients, regardless of gBRCAm status. Funding: Zai Lab (Shanghai) Co., Ltd; National Major Scientific and Technological Special Project for "Significant New Drugs Development" in 2018, China [grant number 2018ZX09736019].

The Pathological Factors Involved in Current In Vitro Atherosclerotic Models.

Cardiovascular disease stemmed from atherosclerosis (AS) is well recognized to be the predominant cause of global death. To comprehensively clarify the pathogenesis of AS, exploit effective drugs, as well as develop therapeutic solutions, various atherosclerotic models were constructed in vitro and widely utilized by the scientific community. Compared with animal models, the in vitro atherosclerotic models play a prominent role not only in the targeted research of single pathological factor related to AS in the human derived system, but also in the combined study on multipathological factors leading to AS, thereby contributing tremendously to the in-depth elucidation of atherosclerotic pathological process. In the current review, a variety of pathological factors incorporated into the existing atherosclerotic models in vitro are broadly elaborated, including the pathological mechanism, in vitro simulation approaches, and the desired improvement perspectives for reproducing each pathological factor. In addition, this review also summarizes the advantages and disadvantages of current atherosclerotic models as well as their potential functionality. Finally, the promising aspects for future atherosclerotic models in vitro with potential advances are also discussed.

A nitrogen-rich graphdiyne containing hexaazatrinaphthylene for high-performance lithium-ion batteries.

A nitrogen-rich graphdiyne (HATN-GDY) material containing electrochemical active hexaazatrinaphthylene units was successfully prepared. HATN-GDY exhibits a superior specific capacity of 2139 mA h g-1 and firm long-term stability due to the unique 2D π-conjugated structure and the large in-plane N-cavities.

Effectiveness of a single low-dose computed tomography screening for lung cancer: A population-based perspective cohort study in China.

The purpose of this perspective cohort study was to evaluate the effectiveness of low-dose computed tomography (LDCT) screening for lung cancer in China. This study was conducted under the China Urban Cancer Screening Program (CanSPUC). The analysis was based on participants aged 40 to 74 years from 2012 to 2019. A total of 255 569 eligible participants were recruited in the study. Among the 58 136 participants at high risk of lung cancer, 20 346 (35.00%) had a single LDCT scan (defined as the screened group) and 37 790 (65.00%) not (defined as the non-screened group). Overall, 1162 participants were diagnosed with lung cancer at median follow-up time of 5.25 years. The screened group had the highest cumulative incidence of lung cancer and the non-screened group had the highest cumulative lung cancer mortality and all-cause cumulative mortality. We performed inverse probability weighting (IPW) to account for potential imbalances, and Cox proportional hazards model to estimate the weighted association between mortality and LDCT scans. After IPW adjusted with baseline characteristics, the lung cancer incidence density was significantly increased (37.0% increase) (HR1.37 [95%CI 1.12-1.69]), lung cancer mortality was decreased (31.0% decrease) (HR0.69 [95%CI 0.49-0.97]), and the all-cause mortality was significantly decreased (23.0% lower) (HR0.77 [95% CI 0.68-0.87]) in the screened group. In summary, a single LDCT for lung cancer screening will reduce the mortality of lung cancer and all-cause mortality in China.

CD48 suppresses proliferation and migration as an immune-related prognostic signature in the cervical cancer immune microenvironment.

Cervical cancer (CC) is one of the most common malignant tumors in gynecology. Immunotherapy and targeted therapy are two particularly effective treatments. In this study, weighted gene co-expression network analysis and CIBERSORT algorithm that quantifies the composition of immune cells were used to analyze CC expression data based on the GEO database and identify modules related to T cells. Five candidate hub genes were identified by tumor-infiltrating immune cells estimation and Kaplan-Meier survival analysis according to CC data from The Cancer Genome Atlas (TCGA). Chemotherapeutic response, methylation, and gene mutation analyses were implemented so that the five candidate hub genes identified may be the potential biomarkers and therapeutic targets which were related to T cell infiltration. Moreover, the results of RT-qPCR revealed that CD48 was a tumor suppressor gene, which was negatively correlated with CC stages, lymph node metastasis, and differentiation. Furthermore, the functional study verified that the interference of CD48 was able to boost the proliferation and migration ability in vitro and the growth of transplanted tumors in vivo. Overall, we identified molecular targets related to immune infiltration and prognosis, regarded CD48 as a key molecule involved in the progression of CC, thus providing new insights into the development of molecular therapy and immunotherapeutics against CC.

Macrocycle-Based Hierarchically Porous Hydrogen-Bonded Organic Frameworks.

Hydrogen-bonded organic frameworks (HOFs) are porous crystalline materials. The pores in HOFs are usually non-covalent extrinsic pores constructed through the formation of the framework. Supramolecular macrocycles with intrinsic pores in their structures are good candidates for constructing HOFs with intrinsic pores from the macrocycles themselves, thus leading to hierarchically porous structures. Combining the macrocycle and HOFs will endow these hierarchically porous materials with enhanced properties and special functionalities. This review summarizes recent advances in macrocycle-based HOFs, including the macrocycles used for constructing HOFs, the hierarchically porous structures of the HOFs, and the applications induced by the hierarchically HOFs porous structures. This review provides insights for future research on macrocycle-based hierarchically porous HOFs and the appropriate applications of the unique structures.

Correlation of clinicopathological and prognostic characteristics between endometriosis-associated and primary ovarian cancer.

BACKGROUND: The main aim of this study was to establish the clinicopathological and prognostic correlations between endometriosis-associated and non-endometriosis-associated primary ovarian cancer, with a view to providing a reference guide for revision of diagnostic criteria for malignant transformation of endometriosis. METHODS: Clinicopathological and follow-up data of 174 patients with clear cell and endometrial ovarian cancer were retrospectively extracted. Cases were divided into endometriosis-associated and non-endometriosis-associated primary ovarian cancer for comparative analysis of clinicopathological characteristics and prognosis. RESULTS: Average age and post-menopausal rate in the endometriosis-associated ovarian cancer group were lower relative to the primary ovarian cancer group (P < 0.05). Body mass index, age at menopause, operation history, dysmenorrhea, complications, tumor size, tumor side, ascites, CA125, HE4, CA19.9, stage, differentiation, expression of ER, PR, P53, P16, Ki67, MMR, HNF-1ß and Napsin A were not significantly different between the groups (P > 0.05). Furthermore, rates of resistance to platinum chemotherapy, relapse, progression-free survival and overall survival were comparable between the two groups (P > 0.05). CONCLUSION: Endometriosis-associated and primary ovarian cancers of the same pathological type are speculated to be homologous in terms of origin from malignant transformation of endometriosis. It may therefore be necessary to revise the diagnostic criteria for ovarian endometriosis malignancy.

Fullerene [60] encapsulated water-soluble supramolecular cage for prevention of oxidative stress-induced myocardial injury.

A water-soluble cube-like supramolecular cage was constructed by an engagement of six molecules through a hydrophobic effect in the water. The obtained cage could perfectly encapsulate one fullerene C60 molecule inside of the cavity and significantly improve the water-solubility of the C60 without changing the original structure. The water-soluble complex was further applied to reduce the reactive oxygen species (R.O.S.) in cardiomyocytes (FMC84) through Akt/Nrf2/HO-1 pathway. Furthermore, in the mouse model of myocardial ischemia-reperfusion injury, the application of C60 was found to be effective in reducing myocardial injury and improving cardiac function. It also reduced the levels of R.O.S. in myocardial tissue, inhibited myocardial apoptosis, and mitigated myocardial inflammatory responses. The present study provides a new guideline for constructing water-soluble C60 and verifies the important role of C60 in preventing oxidative stress-related cardiovascular disease injury.

Short-term outcomes of transvaginal specimen extraction versus transumbilical specimen extraction following totally laparoscopic gastrectomy in female patients with gastric cancer: a retrospective analysis.

Introduction: Natural orifice specimen extraction (NOSE) laparoscopic surgery is emerging as a new and promising technique, especially in gastric cancer (GC). Aim: To analyze the difference between transvaginal and transumbilical specimen extraction following totally laparoscopic gastrectomy (TLG). Material and methods: Between January 2016 and July 2021, 37 consecutive female patients with GC who underwent either natural orifice specimen extraction surgery (NOSES) or TLG at our center were included and analyzed. Results: In total, 12 patients underwent NOSES, and 25 patients underwent TLG. The NOSES group had a shorter operative time (239.3 ±21.5 vs. 256.1 ±21.2 min, p = 0.031) and shorter specimen extraction time (17.0 ±4.2 vs. 30.8 ±4.3 min, p < 0.01). No significant difference was observed in the comparison of the radical validity including estimated blood loss, the number of harvested LNs and the comparisons of distal and proximal margin. In the postoperative recovery comparisons, the NOSES group had a shorter time to first fluids (3.9 ±0.5 vs. 5.6 ±1.2 days, p < 0.01), and time to starting a soft diet (5.6 ±0.7 vs. 7.7 ±1.7 days, p < 0.01). Postoperative pain in the NOSES group was significantly less. Postoperative hospital stay days in the NOSES group were fewer (10.2 ±2.2 vs. 12.4 ±2.9 days, p = 0.030). Overall, the postoperative complications were similar between the two groups (p = 0.438). When more cases were included, the results were similar. NOSES reduced hospital costs for GC patients, and it also applied to the premenopausal patients. Conclusions: NOSES was a safer and more reliable method as compared to transumbilical specimen extraction.

Construction of rigid amine-linked three-dimensional covalent organic frameworks for selectively capturing carbon dioxide.

A highly rigid amine-linked 3D COF was constructed from two orthogonal building blocks (spirobifluorene and bicarbazole) through a post-synthetic chemical reduction. The rigid 3D framework decreased the conformational flexibility of the amine linkages, and thus showed a fully preserved crystallinity and porosity. The amine moieties in the 3D COF afforded abundant chemisorptive sites for selectively capturing CO2.

Structural Regulation of Thiophene-Based Two-Dimensional Covalent Organic Frameworks toward Highly Efficient Photocatalytic Hydrogen Generation.

Two imine-based 2D covalent organic frameworks (COFs) with slight differences in their core structures are presented. The COF containing benzotrithiophene moieties with better planarity and π-conjugation (BTTh-TZ-COF) shows much better photocatalytic activity than the COF with trithienylbenzene cores (TThB-TZ-COF). Further photoelectrochemical study reveals the catalytic mechanism in more detail. Since other factors such as crystallinity, porosity, and optical bandgaps are equal, the different structures of the cores in the two similar COFs are the major contributors to the significantly different photocatalytic performance. The better electron delocalization of the planar trithiophene-based core and the enhanced D-A interactions between the triazine and trithiophene units in BTTh-TZ-COF create efficient charge separation and transfer, thus leading to superior photocatalytic hydrogen evolution activity. A new strategy for preparing high-performance organic photocatalysts for solar-energy conversion is revealed by this study.

A population-based cross-sectional study on the situation of cervical cancer screening in Liaoning, China.

BACKGROUND: Cervical cancer (CC) screening is currently recognized as an effective intervention for CC. Previous studies found that the proportion of screening was low in China, especially in Liaoning. Therefore, we performed a population-based cross-sectional survey to investigate the situation of cervical cancer screening and analyze their related factors for providing a decision-making basis for sustainable and effective development of cervical cancer screening. METHODS: This population-based cross-sectional study involved aged 30 to 69 years in nine counties/districts in Liaoning from 2018 to 2019. Data were collected using the quantitative data collection methods, and analyzed in SPSS version 22.0. RESULTS: Overall, only 22.37% of 5334 respondents reported having ever been screened for cervical cancer in past 3 years, and 38.41% of respondents reported having the willingness for cervical cancer screening in next 3 years. In the rate of CC screening, multilevel analysis indicated that age, marital status, education level, type of occupation, medical insurance, family income, place of residence and regional economic level had a significant impact on proportion of screening. In the rate of CC screening willingness, multilevel analysis indicated that age, family income, health status, place of residence, regional economic level and CC screening still had a significant impact, but marital status, education level and medical insurance type had no significant impact. There was no significant difference in marital status, education level and medical insurance type after the factors of CC screening were added in the model. CONCLUSION: Our study found both proportion of screening and willingness were at a low level, and age, economic and regional factors were the main factors for implementation of CC screening in China. In the future, targeted policies should be formulated according to the characteristics of different groups of people, and reduce the gap in the current health service capacity between different regions.

Comparison between laparoscopic and abdominal radical hysterectomy for cervical adenosquamous carcinoma at stage IA2 to IIA2: A multicenter retrospective study.

OBJECTIVE: We aimed to compare the 5-year oncological outcomes of laparoscopic/abdominal radical hysterectomy (LRH/ARH) in patients with cervical adenosquamous carcinoma at stage IA2 to IIA2 based on the 2009 or 2018 International Federation of Gynecology and Obstetrics (FIGO) staging criteria. METHODS: Based on the clinical diagnosis and treatment of cervical cancer in China (Four C) database, Cox risk regression models were applied to analyze tumor prognosis treated with ARH/LRH in FIGO 2009 and 2018 IA2-IIA2 patients and stratified findings according to tumor diameter (≤4 and >4 cm subgroups). And to avoid bias, propensity score matching (PSM) was also used for the cohort study. RESULTS: Based on FIGO 2009 staging criteria (n = 474), there was no significant difference between the ARH and LRH groups in 5-year disease-free survival (DFS) or overall survival (OS). Lymph node metastasis was a risk factor for 5-year DFS in this stage. After PSM, lymphovascular space invasion (LVSI) was an independent risk factor for 5-year OS in the tumors ≤4 cm subgroup. Based on FIGO2018 staging criteria (n = 322), cervical interstitial infiltration depth was an independent risk factor for 5-year OS in the total population and the tumor diameter ≤4 cm subgroup. CONCLUSIONS: Laparoscopic surgery was not a risk factor affecting the oncologic prognosis of adenosquamous carcinoma of the cervix based on either FIGO 2009 or 2018 staging of stage IA2-IIA2. In addition, LRH may be considered for patients with early-stage cervical adenosquamous carcinoma.

Rigid-Flexible Hybrid Porous Molecular Crystals with Guest-Induced Reversible Crystallinity.

A weak CH/O hydrogen-bonded organic framework (HOF) with both rigidity and flexibility that could easily and reversibly switch from a non-crystalline to a crystalline phase was constructed. The specific solvent molecule acts as a "key" to control the crystallinity, while the highly rigid triangle macrocycle as the building block is the "lock". The introduction and removal of the "key" could influence the local flexibility of the whole framework and lead to switchable crystallinity. Furthermore, the obtained HOF exhibits excellent separation efficiency for benzene and cyclohexane (94.4 %).

A Bayesian network predicting survival of cervical cancer patients-Based on surveillance, epidemiology, and end results.

This study aimed to build a comprehensive model for predicting the overall survival (OS) of cervical cancer patients who received standard treatments and to build a series of new stages based on the International Federation of Gynecologists and Obstetricians (FIGO) stages for better such predictions. We collected the cervical cancer patients diagnosed since the year 2000 from the Surveillance, Epidemiology, and End Results (SEER) database. Cervical cancer patients who received radiotherapy or surgery were included. Log-rank tests and Cox regression were used to identify potential factors of OS. Bayesian networks (BNs) were built to predict 3- and 5-year survival. We also grouped the patients into new stages by clustering their 5-year survival probabilities based on FIGO stage, age, and tumor differentiation. Cox regression suggested black ethnicity, adenocarcinoma, and single status as risks for poorer prognosis, in addition to age and stage. A total of 43,749 and 39,333 cases were finally eligible for the 3- and 5-year BNs, respectively, with 11 variables included. Cluster analysis and Kaplan-Meier curves indicated that it was best to divide the patients into nine modified stages. The BNs had excellent performance, with area under the curve and maximum accuracy of 0.855 and 0.804 for 3-year survival, and 0.851 and 0.787 for 5-year survival, respectively. Thus, BNs are excellent candidates for predicting cervical cancer survival. It is necessary to consider age and tumor differentiation when estimating the prognosis of cervical cancer using FIGO stages.

Neoadjuvant chemotherapy for patients with international federation of gynecology and obstetrics stages IB3 and IIA2 cervical cancer: a multicenter prospective trial.

BACKGROUND: Preoperative neoadjuvant chemotherapy (NACT) has been widely used in developing countries for the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB3 and IIA2 cervical cancer. However, the effectiveness of NACT and treatment options for NACT-insensitive patients have been concerning. This study will assess prognostic differences between NACT and primary surgery treatment (PST), determine factors associated with prognosis, and explore better adjuvant treatment modalities for NACT-insensitive patients. METHODS: This study analyzed clinical characteristics, pathological characteristics, treatment options, and follow-up information of 774 patients with FIGO stages IB3 and IIA2 cervical cancer from 28 centers from January 2016 to October 2019 who participated in a multicenter, prospective, randomized controlled trial. RESULTS: For patients undergoing NACT, the 5-year OS and PFS rate was 85.8 and 80.5% respectively. They were similar in the PST group. There was no significant difference in OS and PFS between clinical response (CR)/partial response (PR) groups and stable disease (SD)/progressive disease (PD) groups. Apart from deep cervical invasion (p = 0.046) affecting OS for patients undergoing NACT, no other clinical and pathological factors were associated with OS. 97.8% of NACT-insensitive patients opted for surgery. If these patients did not have intermediate- or high-risk factors, whether they had undergone postoperative adjuvant therapy was irrelevant to their prognosis, whereas for patients with intermediate- or high-risk factors, adjuvant chemotherapy resulted in better PFS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.019) and OS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.002). CONCLUSIONS: NACT could be a choice for patients with FIGO stages IB3 and IIA2 cervical cancer. The main risk factor influencing prognosis in the NACT group is deep cervical invasion. After systematic treatment, insensitivity to NACT does not indicate a poorer prognosis. For NACT-insensitive patients, Chinese prefer surgery. Postoperative adjuvant therapy in patients with no intermediate- or high-risk factors does not improve prognosis, and chemotherapy in patients with intermediate- and high-risk factors is more effective than radiation therapy and other treatments. TRIAL REGISTRATION: The study was prospectively registered on ClinicalTrials.gov (NCT03308591); date of registration: 12/10/2017.

Efficacy and Safety of the Anti-PD-L1 mAb Socazolimab for Recurrent or Metastatic Cervical Cancer: a Phase I Dose-Escalation and Expansion Study.

PURPOSE: This study (ClinicalTrials.gov identifier, NCT03676959) is an open, phase I dose-escalation and expansion study investigating the safety and efficacy of the recombinant, fully human anti-programmed death ligand 1 (PD-L1) mAb socazolimab in patients diagnosed with recurrent or metastatic cervical cancer. PATIENTS AND METHODS: Patients received socazolimab every 2 weeks until disease progression. The study was divided into a dose-escalation phase and a dose-expansion phase. Safety and tolerability were primary endpoints of the dose-escalation phase. The primary endpoints of the dose-expansion phase were safety and the objective response rate (ORR) of the 5 mg/kg dose. Efficacy was assessed by the third-party independent review committee (IRC) using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). RESULTS: 104 patients were successfully enrolled into the study. Twelve patients were included in the dose-escalation phase, with one complete response and two partial responses in the 5 mg/kg treatment group. Ninety-two patients (5 mg/kg) were enrolled in the dose-expansion phase. Fifty-four patients (59.3%) had baseline PD-L1-positive tumor expression (combined positive score ≥1). ORR was 15.4% [95% confidence interval (CI), 8.7%-24.5%]. Median PFS was 4.44 months (95% CI, 2.37-5.75 months), and the median OS was 14.72 months (95% CI, 9.59-NE months). ORR of PD-L1-positive patients was 16.7%, and the ORR of PD-L1-negative patients was 17.9%. No treatment-related deaths occurred. CONCLUSIONS: Our study demonstrates that socazolimab has durable safety and efficacy for the treatment of recurrent or metastatic cervical cancer and exhibits a safety profile similar to other anti-PD-1/PD-L1 mAbs.

Local Label Point Correction for Edge Detection of Overlapping Cervical Cells.

Accurate labeling is essential for supervised deep learning methods. However, it is almost impossible to accurately and manually annotate thousands of images, which results in many labeling errors for most datasets. We proposes a local label point correction (LLPC) method to improve annotation quality for edge detection and image segmentation tasks. Our algorithm contains three steps: gradient-guided point correction, point interpolation, and local point smoothing. We correct the labels of object contours by moving the annotated points to the pixel gradient peaks. This can improve the edge localization accuracy, but it also causes unsmooth contours due to the interference of image noise. Therefore, we design a point smoothing method based on local linear fitting to smooth the corrected edge. To verify the effectiveness of our LLPC, we construct a largest overlapping cervical cell edge detection dataset (CCEDD) with higher precision label corrected by our label correction method. Our LLPC only needs to set three parameters, but yields 30-40% average precision improvement on multiple networks. The qualitative and quantitative experimental results show that our LLPC can improve the quality of manual labels and the accuracy of overlapping cell edge detection. We hope that our study will give a strong boost to the development of the label correction for edge detection and image segmentation. We will release the dataset and code at: https://github.com/nachifur/LLPC.

PM2.5 exposure and cervical cancer survival in Liaoning Province, northeastern China.

Particulate matter with a diameter of 2.5 µm or less (PM2.5) has frequently been reported to be associated with an increased incidence of cancer, but few studies have explored the association between PM2.5 exposure and cancer survival. We retrospectively analyzed the association between PM2.5 exposure and the overall survival (OS) of cervical cancer patients residing in 14 urban areas of Liaoning Province, northeastern China, during January 2014-October 2021. Patients from urban areas who completed the recommended treatments with complete follow-up information were included. The PM2.5 monitoring data of each urban area of Liaoning Province were retrieved, and individual exposure to PM2.5 after diagnosis was calculated as the average daily concentration in the city of residence from the date of discharge to the date of death or the last follow-up. Log-rank tests and Cox regression were performed to examine the relationship between PM2.5 exposure and cervical cancer survival. A total of 1753 cervical cancer patients were finally included, among whom 804 (45.9%) were from Shenyang City, the capital of Liaoning Province. The median average daily concentration of PM2.5 to which the patients were exposed was 45.0 (interquartile range 38.2-50.0) µg/m3. Both log-rank tests (grouped by quartiles, p < 0.001) and Cox regression (continuous, HR = 1.06, 95% CI 1.04-1.08) indicated that PM2.5 was significantly associated with shorter OS. Sensitivity analysis also confirmed the robustness of our findings. From the subgroup analysis, only the OS of stage II and stage III patients was associated with PM exposure. Our findings provide the insight that PM2.5 exposure might be associated with shorter OS of cervical cancer patients.