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The restricted mean survival time measure has gained a lot of interests for designing and analyzing oncology trials with time-to-event endpoints due to its intuitive clinical interpretation and potentially high statistical power. In the non-inferiority trial literature, restricted mean survival time has been used as an alternative measure for reanalyzing a completed trial, which was originally designed and analyzed based on traditional proportional hazard model. However, the reanalysis procedure requires a conversion from the non-inferiority margin measured in hazard ratio to a non-inferiority margin measured by restricted mean survival time difference. An existing conversion method assumes a Weibull distribution for the population survival time of the historical active control group under the proportional hazard assumption using data from a single trial. In this article, we develop a methodology for non-inferiority margin conversion when data from multiple historical active control studies are available, and introduce a Kaplan-Meier estimator-based method for the non-inferiority margin conversion to relax the parametric assumption. We report extensive simulation studies to examine the performances of proposed methods under the Weibull data generative models and a piecewise-exponential data generative model that mimic the tumor recurrence and survival characteristics of advanced colon cancer. This work is motivated to achieve non-inferiority margin conversion, using historical patient-level data from a large colon cancer clinical database, to reanalyze an internationally collaborated non-inferiority study that evaluates 6-month versus 3-month duration of adjuvant chemotherapy in stage III colon cancer patients.

The inhibition of function-specific β-N-acetyl-D-hexosaminidases, such as OfHex1 from the Asian corn borer (Ostrinia furnacalis), is a promising strategy for the development of green pesticides. Among reported OfHex1 inhibitors, glycosyl inhibitors show especially high inhibitory activity. In this study, a series of novel C-glycosidic oximino carbamate derivatives were designed using the OfHex1 crystal structure and synthesized. Among the C-Glycoside derivatives studied, compound 7k exhibited the best inhibitory activity against OfHex1 (IC

Purpose To investigate whether the assisted reproductive technology (ART) outcome differed amongst women with primary and recurrent endometriomas and to identify prognostic factors for a poor cumulative live birth rate (cLBR) in women with severe endometriosis by a retrospective cohort analysis. Methods A total of 836 patients with stage Ⅲ and Ⅳ ovarian endometriosis were included; of which 734 women without and 102 with recurrent endometrioma underwent 1048 ART cycles. The main outcome measures were cumulative clinical pregnancy rate (cPR) and cLBR per cycle. Prognostic factors of ART outcome were identified by comparing women who became pregnant with those who did not, using univariate and adjusted multiple logistic regression models. Results In all, 549 (65.67%) women became pregnant and 507 (60.65%) had a live birth. The cumulative cPR and LBR per cycle were 54.20% and 48.38%, respectively. In the recurrent group, the antral follicle count (AFC) and number of retrieved oocytes were lower than for women with primary endometriomas. However, the cLBR were similar between the two groups. Further, after multivariate analysis, ages ≥35 y and time interval ≥2 y between surgery and ART were independent factors associated with lower cLBR in patients with severe endometriosis. Number of surgeries ≥2 and lower AFC were also associated with negative ART outcomes. Conclusion An advanced maternal age, an altered ovarian reserve, number of surgeries, and/or longer interval between surgery and ART had a negative impact on ART cLBR for infertile women with rAFS stage Ⅲ and Ⅳ ovarian endometriosis. Retrospective trial registration number : IRB-20210319-R, date of registration: 4.10.2021

Cone-beam computed tomography (CBCT) is one of the most widely used digital models in dental practices. A critical step in virtual dental treatment planning is to accurately delineate all tooth-bone structures from CBCT with high fidelity. Previous studies have established several methods for CBCT segmentation using deep learning. However, the inherent resolution discrepancy and the loss of occlusal information in CBCT largely limited its clinical applicability. Here, we present a Deep Dental Multimodal Analysis (DDMA) framework consisting of a CBCT segmentation model, an intraoral scan (IOS) segmentation model (the most accurate digital dental model), and a fusion model to generate 3D fused tooth-bone structures with high fidelity and accurate occlusal information. Our model was trained with a large-scale dataset with 503 CBCT and 28,559 IOS meshes manually annotated by human experts. For CBCT segmentation, our framework achieves an average Dice coefficient of 93.99%, significantly outperforming the baselines. For IOS segmentation, our model achieves a mIoU of 93.07% and 95.70% on the maxillary and mandible on a test dataset of 200 IOS meshes, 1.77% and 3.52% higher than the state-of-art method. In addition, our DDMA framework takes 20 to 25 minutes to generate the fused model, compared to over 5 hours by human experts. Notably, real-world clinical cases demonstrate that our model can visualize tooth-bone structures and relationships during the entire orthodontic treatment and predict clinical risks like dehiscence and fenestration. These findings demonstrate the potential of deep multimodal learning to improve the quality of digital dental models and guide clinical treatment and diagnostic decisions.

Photodynamic therapy (PDT) is a potential way for the tumor treatment. However, it notably suffers the limitation of hypoxia in solid tumors. Thus, it is significant to develop effective photosensitizers which can exhibit excellent therapeutic performance under both normoxia and hypoxia. Herein, we reported four ionic iridium(III) complexes ( Ir1 – Ir4 ) with anthraquinone groups which can regulate their excited state energy levels effectively. Among them, the energy gap of Ir1 was between 1.63 and 2.21 eV, which can match well with that of O2, and the HOMO energy of Ir1 is less than −5.51 eV. Compared with Ir2 – Ir4 , the luminescent quantum efficiency of Ir1 was the highest. Particularly, Ir1 can specifically target the mitochondria of the tumor cells. Meanwhile, Ir1 showed high singlet oxygen quantum yields ( Φ Δ) in both solutions and living cells with low cytotoxicity. The results of PDT experiments revealed that Ir1 , as a photosensitizer, exhibited excellent therapeutic effect not only in normoxia but also in hypoxia condition. We believe that this work is meaningful for developing excellent PDT agents based on cyclometalated Ir(III) complexes via rational ligand modification.

To investigate the effect of cervical cerclage or conservative treatment on maternal and neonatal outcomes in singleton gestations with a sonographic short cervix, and further compare the relative treatment value. A retrospective study was conducted among women with singleton gestations who had a short cervical length (

In this paper, the kernel principal component analysis (KPCA) is applied to perform the translation quality classification and evaluation of human-machine composite subject of scientific text. Firstly, four different translations are quantified by means of questionnaire survey according to the basic standards of Chinese-English translation. Then, the quantitative data is evaluated by Gaussian kernel function and polynomial kernel function. The results show that, on the one hand, the translation qualities of machine translation, professional translator and scientific researcher approximate to form an equilateral triangle in two-dimensional evaluation space, which indicates that the qualities of the above three translations is independent of each other in terms of evaluation space, and the translation quality of computer-aided scientific researcher is closest to the translation quality of professional translator; on the other hand, when the evaluation space dimension is reduced to one-dimensional, Gaussian kernel function can still get similar result, but polynomial kernel function gives different result when its order is greater than a certain threshold.

Genping Huang,1,* Ruizhe Chen,1,* Nanjia Lu,1 Qin Chen,2 Weiguo Lv,1,3 Baohua Li1,3 1Department of Gynecologic Oncology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Pathology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 3Center of Uterine Cancer Diagnosis & Therapy of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Baohua LiDepartment of Gynecologic Oncology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, People’s Republic of ChinaTel +86 571 87061501Fax +86 571 87061878Email lbh19787@zju.edu.cnPurpose: There is currently a lack of research on preoperative prognostic analysis of early-stage cervical adenocarcinoma (ADC). The purpose of our study was to clarify whether preoperative serum tumor-marker levels were of prognostic value in early-stage ADC.Patients and Methods: We performed a retrospective study of patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA1–IIA1 and pathology-proven invasive ADC. We evaluated the relationship between preoperative serum tumor-marker levels and clinicopathological characteristics, and identified the relative preoperative risk factors affecting disease-free survival (DFS) and overall survival (OS). The optimal cut-off point of meaningful tumor markers was determined by the analysis of receiver operating characteristics (ROC), and the accuracy of the results was evaluated by the area under the curve (AUC).Results: Elevated carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), squamous cell carcinoma antigen (SCC-Ag), alpha-fetoprotein (AFP), carbohydrate antigen 153 (CA153) and carbohydrate antigen 199 (CA199) were associated with certain clinicopathologic features of early-stage ADC. The combination of elevated serum CEA and CA125 was significantly associated with FIGO stage, body mass index (BMI) and LNM. Kaplan–Meier survival curve and Cox regression analyses revealed that CEA and CA125 might have significant prognostic implications in early-stage ADC patients, and the combination of elevated serum CEA and CA125 served as an independent predictor of early-stage ADC. The optimal cut-off point of serum CA125 for prediction DFS and OS was 32.60 U/mL and of serum CEA were 2.85 ng/mL and 2.05 ng/mL, respectively. The AUC showed that serum CEA was a moderate predictor of OS.Conclusion: The preoperative serum levels of CEA and CA125 might have significant prognostic implications in early-stage ADC patients. Combined preoperative serum CEA and CA125 levels independently predicted the prognosis of early-stage ADC.Keywords: the early-stage cervical adenocarcinoma, carcinoembryonic antigen, cancer antigen 125, prognosis

Xiaoyu Tu,1,* Ruizhe Chen,1,* Genping Huang,1 Nanjia Lu,1 Qin Chen,2 Xiaoxia Bai,1 Baohua Li1 1Department of Gynecologic Oncology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Pathology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Baohua Li Email lbh19787@zju.edu.cnPurpose: To investigate the potential factors to predict severe myelosuppression among low-risk gestational trophoblastic neoplasia (GTN) patients with single-agent methotrexate (MTX) chemotherapy. To analyze reproductive outcomes of patients with or without severe myelosuppression after achieving complete remission (CR).Patients and Methods: The retrospective study included 319 low-risk GTN patients registered from January 2008 to December 2018 in our hospital. Patients were divided into two groups according to myelosuppression grading. Their clinical data and reproductive outcomes were compared and analyzed.Results: A higher proportion of patients in group A received second-line chemotherapy than group B (P< 0.001). The number of total chemotherapy courses was more in group A than group B (P=0.001), while the number of MTX chemotherapy courses was more in group B than group A (P=0.001). When the joint predictor of pretreatment albumin (ALB) was not more than 44.5 g/L, pretreatment serum creatinine (Scr) was not less than 75.6 μmol/L, and the number of MTX chemotherapy courses was not less than four, there was a moderate predictive value. There was no significant difference of reproductive outcomes between the two groups after achieving CR.Conclusion: Although some patients developed severe myelosuppression, MTX was still the effective first-line treatment for low-risk GTN patients. Patient’s pretreatment ALB was not more than 44.5 g/L, pretreatment Scr was not less than 75.6 μmol/L, and the number of MTX chemotherapy courses not less than four could be used as combined predictors to recognize the risk of severe myelosuppression. Severe myelosuppression had no significant adverse influence on fertility after achieving CR.Keywords: gestational trophoblastic neoplasia, methotrexate, myelosuppression, fertility

BACKGROUND This study was aimed to investigate the relationship between 25-hydroxy vitamin D (25(OH)D) level and the occurrence of pre-eclampsia (PE) and also the risk factors of developing early and late onset PE. METHODS A total of 370 pregnant women were included between January 2015 and December 2016 at our hospital. PE was defined as the presence of maternal blood pressure > 140/90 mmHg and 24-hour proteinuria levels > 300 mg or 2 + in a random sample of urine after the 20th week of pregnancy. Controls were pregnant women without hypertension and proteinuria. Assessment of 25(OH)D was performed at 16 - 20 weeks of gestation. Univariate and multivariate analyses were used to evaluate the association of vitamin D with PE. RESULTS There were 201 patients with PE while 169 pregnant women were controls. Patients with PE had older maternal age (p < 0.001), earlier gestation age (p < 0.001), and higher systolic blood pressure (SBP) and diastolic blood pressure (DBP) (p < 0.001). The level of 25(OH)D in the PE group (17.26 ± 13.95 µg/L) was significantly lower than that in controls (22.15 ± 12.65 µg/L, p = 0.019). Moreover, the proportion of 25(OH)D deficiency in patients with PE was significantly higher than that of controls (27.6% vs. 0.9%, p < 0.001). Older age, high SBP, and low level of 25(OH)D were independent risk factors of both early and late onset PE during pregnancy. CONCLUSIONS Low 25(OH)D level was more likely presented in PE patients and was an independent risk factor of both early and late onset PE.

In this work, MnO2 nanosheets arrays vertically grown on nickel foam have been fabricated, and the concentration of oxygen vacancies has increased through electrooxidation treatment. The abundant oxygen vacancies facilitated electron transfer which helps to enhance the conductivity of active material. Besides, the novel porous structure with large surface area and rich Mn3+ catalytic active sites benefit the efficient OER activity. The binder-free VO-MnO2-NF electrode was directly applied for oxygen evolution reaction, which exhibited a compatible overpotential of 0.27 V at 10 mA cm−2 and excellent electrochemistry stability with neglectable potential change for 12 h.

Adaptive enrichment designs (AEDs) of clinical trials allow investigators to restrict enrollment to a promising subgroup based on an interim analysis. Most of the existing AEDs deal with a small number of predefined subgroups, which are often unknown at the design stage. The newly developed Simon design offers a great deal of flexibility in subgroup selection (without requiring pre-defined subgroups) but does not provide a procedure for estimating and testing treatment efficacy for the selected subgroup. This article proposes a 2-stage AED which does not require predefined subgroups but requires a prespecified algorithm for choosing a subgroup on the basis of baseline covariate information. Having a prespecified algorithm for subgroup selection makes it possible to use cross-validation and bootstrap methods to correct for the resubstitution bias in estimating treatment efficacy for the selected subgroup. The methods are evaluated and compared in a simulation study mimicking actual clinical trials of human immunodeficiency virus infection.

Introduction: Approximately 1,000 out-of-hospital cardiac arrest (OHCA) occur per day in the United States. Although survival rates remains low, the extent to which OHCA neurological outcomes differ between men and women remains poorly characterized. Methods: Within the national Cardiac Arrest Registry to Enhance Survival (CARES) registry, we identified 195,722 adult individuals with an OHCA between 2013-2017. Using multi-variable logistic regression models, we evaluated for sex differences in rates of survival to hospital discharge and favorable neurological outcome (survival with discharge CPC score of 1 or 2), adjusted for cardiac arrest characteristics, race, location, year of arrest, age, and use of targeted temperature management (TTM) and coronary angiography. Results: Overall, 70,767 (31%) patients were women. Median age was 64 and 62 years for women and men, respectively. An initial shockable rhythm (14.9% vs. 25.7%) and a witnessed arrest (40.9% vs. 45.6%) was more common in men. Bystander CPR was provided to 37% of women and 39% of men. Men were less likely to survive to hospital discharge than women (8.7% vs. 10.9%; adjusted OR 0.75, 95% CI 0.73, 0.78). Similarly, men were less likely to have favorable neurological outcome (6.6% vs. 9.2% for women; adjusted OR 0.78, 95% CI 0.74, 0.82). Further interaction analysis for the pre-hospital elements found small, but statistically significant sex differences in favorable neurological survival for witnessed status (among female OR 2.29, 95% CI 2.10, 2.49; among males OR 2.07, 95% CI 1.92, 2.23, p= 0.04) and for bystander CPR (among females OR 1.20, 95% CI 1.11, 1.29; among males OR 1.34, 95% CI 1.27, 1.42, p= 0.01). Interaction of sex with the hospital level variables of TTM and coronary angiography, for the subset of patients that survived to hospital admission, had no sex differences in favorable neurological outcome. Conclusion: Our analysis shows that for OHCA in the United States, women have better survival outcomes than men. There was a sex differences in the pre-hospital variable of BCPR, but not in the other modifiable variables of TTM and coronary angiography. Further study is needed to better understand sex differences in overall survival and neurological outcomes.

A novel chemiluminescence resonance energy transfer (CRET) system was developed and combined with a structure-switching aptamer for the highly sensitive detection of platinum. Platinum was chosen as a model analyte to demonstrate the generality of the new CRET system. This aptameric platform consisted of a streptavidin labeled aptamer against platinum and a streptavidin-coated magnetic bead for the selective separation of platinum-bound aptamer. The platinum–aptamer probe contained several guanine (G) bases bound to the 3,4,5-trimethoxyphenyl-glyoxal (TMPG) donor group at the 5′ end, a fluorescent acceptor (6-carboxy-2′,4,7,7′-tetrachlorofluorescein, TET) at the 3′ end, and a streptavidin aptamer sequence in which several base pairs were replaced by the G-G mismatch to induce the platinum-oligonucleotide coordination. The chemiluminescence (CL) generated by TMPG/G bases is transferred to the acceptor (TET). In the presence of platinum, the platinum–aptamer probe was folded such that the G bases at the 5′ end and TET at the 3′ were in close proximity. The complex was separated using streptavidin-coated magnetic beads by the addition of TMPG to form the TMPG/G bases complex. The ultraweak CL from the TMPG/G bases was strongly enhanced by TET. This novel CRET-based method can be easily performed with high limit of detection (50 ng·mL−1) and selectivity over other metal ions. This technique provides a novel method for simple, fast, and convenient point-of-care diagnostics for monitoring proteins and metal ions.

Adaptive enrichment designs (AEDs) of clinical trials allow investigators to restrict enrollment to a promising subgroup based on an interim analysis. Most of the existing AEDs deal with a small number of predefined subgroups, which are often unknown at the design stage. The newly developed Simon design offers a great deal of flexibility in subgroup selection (without requiring pre-defined subgroups) but does not provide a procedure for estimating and testing treatment efficacy for the selected subgroup. This article proposes a 2-stage AED which does not require predefined subgroups but requires a prespecified algorithm for choosing a subgroup on the basis of baseline covariate information. Having a prespecified algorithm for subgroup selection makes it possible to use cross-validation and bootstrap methods to correct for the resubstitution bias in estimating treatment efficacy for the selected subgroup. The methods are evaluated and compared in a simulation study mimicking actual clinical trials of human immunodeficiency virus infection.