Peritumoral MRI Radiomics Features Increase the Evaluation Efficiency for Response to Chemotherapy in Patients With Epithelial Ovarian Cancer.

BACKGROUND: It remains unclear whether extracting peritumoral volume (PTV) radiomics features are useful tools for evaluating response to chemotherapy of epithelial ovarian cancer (EOC). PURPOSE: To evaluate MRI radiomics signatures (RS) capturing subtle changes of PTV and their added evaluation performance to whole tumor volume (WTV) for response to chemotherapy in patients with EOC. STUDY TYPE: Retrospective. POPULATION: 219 patients aged from 15 to 79 years were enrolled. FIELD STRENGTH/SEQUENCE: 3.0 or 1.5T, axial fat-suppressed T2-weighted imaging (FS-T2WI), diffusion-weighted imaging (DWI), and contrast enhanced T1-weighted imaging (CE-T1WI). ASSESSMENT: MRI features were extracted from the four axial sequences and six different volumes of interest (VOIs) (WTV and WTV + PTV (WPTV)) with different peritumor sizes (PS) ranging from 1 to 5 mm. Those features underwent preprocessing, and the most informative features were selected using minimum redundancy maximum relevance and least absolute shrinkage and selection operator to construct the RS. The optimal RS, with the highest area under the curve (AUC) of receiver operating characteristic was then integrated with independent clinical characteristics through multivariable logistic regression to construct the radiomics-clinical model (RCM). STATISTICAL TESTS: Mann-Whitney U test, chi-squared test, DeLong test, log-rank test. P < 0.05 indicated a significant difference. RESULTS: All the RSs constructed on WPTV exhibited higher AUCs (0.720-0.756) than WTV (0.671). Of which, RS with PS = 2 mm displayed a significantly better performance (AUC = 0.756). International Federation of Gynecology and Obstetrics (FIGO) stage was identified as the exclusive independent clinical evaluation characteristic, and the RCM demonstrated higher AUC (0.790) than the RS, but without statistical significance (P = 0.261). DATA CONCLUSION: The radiomics features extracted from PTV could increase the efficiency of WTV radiomics for evaluating the chemotherapy response of EOC. The cut-off of 2 mm PTV was a reasonable value to obtain effective evaluation efficiency. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

Deep Learning Nomogram for the Identification of Deep Stromal Invasion in Patients With Early-Stage Cervical Adenocarcinoma and Adenosquamous Carcinoma: A Multicenter Study.

BACKGROUND: Deep stromal invasion (DSI) is one of the predominant risk factors that determined the types of radical hysterectomy (RH). Thus, the accurate assessment of DSI in cervical adenocarcinoma (AC)/adenosquamous carcinoma (ASC) can facilitate optimal therapy decision. PURPOSE: To develop a nomogram to identify DSI in cervical AC/ASC. STUDY TYPE: Retrospective. POPULATION: Six hundred and fifty patients (mean age of 48.2 years) were collected from center 1 (primary cohort, 536), centers 2 and 3 (external validation cohorts 1 and 2, 62 and 52). FIELD STRENGTH/SEQUENCE: 5-T, T2-weighted imaging (T2WI, SE/FSE), diffusion-weighted imaging (DWI, EPI), and contrast-enhanced T1-weighted imaging (CE-T1WI, VIBE/LAVA). ASSESSMENT: The DSI was defined as the outer 1/3 stromal invasion on pathology. The region of interest (ROI) contained the tumor and 3 mm peritumoral area. The ROIs of T2WI, DWI, and CE-T1WI were separately imported into Resnet18 to calculate the DL scores (TDS, DDS, and CDS). The clinical characteristics were retrieved from medical records or MRI data assessment. The clinical model and nomogram were constructed by integrating clinical independent risk factors only and further combining DL scores based on primary cohort and were validated in two external validation cohorts. STATISTICAL TESTS: Student's t-test, Mann-Whitney U test, or Chi-squared test were used to compare differences in continuous or categorical variables between DSI-positive and DSI-negative groups. DeLong test was used to compare AU-ROC values of DL scores, clinical model, and nomogram. RESULTS: The nomogram integrating menopause, disruption of cervical stromal ring (DCSRMR), DDS, and TDS achieved AU-ROCs of 0.933, 0.807, and 0.817 in evaluating DSI in primary and external validation cohorts. The nomogram had superior diagnostic ability to clinical model and DL scores in primary cohort (all P < 0.0125 [0.05/4]) and CDS (P = 0.009) in external validation cohort 2. DATA CONCLUSION: The nomogram achieved good performance for evaluating DSI in cervical AC/ASC. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Intratumoral and peritumoral MRI radiomics nomogram for predicting parametrial invasion in patients with early-stage cervical adenocarcinoma and adenosquamous carcinoma.

OBJECTIVE: To develop a comprehensive nomogram based on MRI intra- and peritumoral radiomics signatures and independent risk factors for predicting parametrial invasion (PMI) in patients with early-stage cervical adenocarcinoma (AC) and adenosquamous carcinoma (ASC). METHODS: A total of 460 patients with IB to IIB cervical AC and ASC who underwent preoperative MRI examination and radical trachelectomy/hysterectomy were retrospectively enrolled and divided into primary, internal validation, and external validation cohorts. The original (Ori) and wavelet (Wav)-transform features were extracted from the volumetric region of interest of the tumour (ROI-T) and 3mm- and 5mm-peritumoral rings (ROI-3 and ROI-5), respectively. Then the Ori and Ori-Wav feature-based radiomics signatures from the tumour (RST) and 3 mm- and 5 mm-peritumoral regions (RS3 and RS5) were independently built and their diagnostic performances were compared to select the optimal ones. Finally, the nomogram was developed by integrating optimal intra- and peritumoral signatures and clinical independent risk factors based on multivariable logistic regression analysis. RESULTS: FIGO stage, disruption of the cervical stromal ring on MRI (DCSRMR), parametrial invasion on MRI (PMIMR), and serum CA-125 were identified as independent risk factors. The nomogram constructed by integrating independent risk factors, Ori-Wav feature-based RST, and RS5 yielded AUCs of 0.874 (0.810-0.922), 0.885 (0.834-0.924), and 0.966 (0.887-0.995) for predicting PMI in the primary, internal and external validation cohorts, respectively. Furthermore, the nomogram was superior to radiomics signatures and clinical model for predicting PMI in three cohorts. CONCLUSION: The nomogram can preoperatively, accurately, and noninvasively predict PMI in patients with early-stage cervical AC and ASC. CLINICAL RELEVANCE STATEMENT: The nomogram can preoperatively, accurately, and noninvasively predict PMI and facilitate precise treatment decisions regarding chemoradiotherapy or radical hysterectomy in patients with early-stage cervical AC and ASC. KEY POINTS: The accurate preoperative prediction of PMI in early-stage cervical AC and ASC can facilitate precise treatment decisions regarding chemoradiotherapy or radical hysterectomy. The nomogram integrating independent risk factors, Ori-Wav feature-based RST, and RS5 can preoperatively, accurately, and noninvasively predict PMI in early-stage cervical AC and ASC. The nomogram was superior to radiomics signatures and clinical model for predicting PMI in early-stage cervical AC and ASC.

The impact of spectacle correction on the well-being of children with vision impairment due to uncorrected refractive error: a systematic review.

BACKGROUND: Despite being easily corrected with eyeglasses, over two-thirds of the world's child population presents with vision impairment (VI) due to uncorrected refractive errors. While systematic reviews have shown that VI can significantly impact children's depression and anxiety, none have reviewed the existing literature on the association between spectacle correction and well-being. This review aims to address this knowledge gap. MAIN OUTCOME MEASURES: The main outcome measures were i) cognitive and education well-being which included mathematics and english literacy, reading fluency, school function, academic performance and grades; ii) psychological and mental health well-being which included physical anxiety, learning anxiety and mental health test scores and iii) quality of life. METHODS: We searched eight databases for articles published between 1999 to 2021 that assessed the associations between spectacle correction and children's (0 to 18 years) well-being. There were no restrictions on language or geographic location. Two reviewers independently screened all publications using validated quality checklists. The findings of the review were analysed using narrative synthesis. [PROSPERO CRD42020196847]. RESULTS: Of 692 records found in the databases, six randomised control trials, one cohort, one cross-sectional and one qualitative study (N = 9, 1.3%) were eligible for analysis. Data were collected from 25 522 children, 20 parents and 25 teachers across the nine studies. Seven were rated as good quality (67 to 100% of quality criteria fulfilled), and two were satisfactory (33 to 66% of quality criteria fulfilled). Spectacle correction was found to improve children's educational well-being (n = 4 very strong evidence; n = 2 strong evidence), quality of life (n = 1, very strong evidence) and decrease anxiety and increase mental health scores (n = 1, strong evidence). CONCLUSION: Evidence suggests that spectacle correction improves children's cognitive and educational well-being, psychological well-being, mental health, and quality of life. More research is needed, given the paucity of published literature and the focus on only three aspects of well-being.

Comparative transcriptomic analysis of the super hybrid rice Chaoyouqianhao under salt stress.

BACKGROUND: Soil salinization is a threat to food security. China is rich in saline land resources for potential and current utilization. The cultivation and promotion of salt-tolerant rice varieties can greatly improve the utilization of this saline land. The super hybrid rice Chaoyouqianhao (CY1000) is one of the most salt-tolerant rice varieties and is widely used, but the molecular mechanism underlying its salt tolerance is not clear. RESULTS: In this study, the characteristics of CY1000 and its parents were evaluated in the field and laboratory. The results showed that aboveground parts of CY1000 were barely influenced by salt stress, while the roots were less affected than those of its parents. A comparative transcriptomic strategy was used to analyze the differences in the response to salt stress among the male and female parents of CY1000 at the seedling stage and the model indica rice 93-11. We found that the salt tolerance of CY1000 was mainly inherited from its male parent R900, and its female parent GX24S showed hardly any salt tolerance. To adapt to salt stress, CY1000 and R900 upregulated the expression of genes associated with soluble component synthesis and cell wall synthesis and other related genes and downregulated the expression of most genes related to growth material acquisition and consumption. In CY1000 and R900, the expression of genes encoding some novel key proteins in the ubiquitination pathway was significantly upregulated. After treatment with MG-132, the salt tolerance of CY1000 and R900 was significantly decreased and was almost the same as that of the wild type after salt stress treatment, indicating that ubiquitination played an important role in the salt tolerance mechanism of CY1000. At the same time, we found that some transcription factors were also involved in the salt stress response, with some transcription factors responding only in hybrid CY1000, suggesting that salt tolerance heterosis might be regulated by transcription factors in rice. CONCLUSION: Our results revealed that the ubiquitination pathway is important for salt tolerance in rice, and several novel candidate genes were identified to reveal a novel salt tolerance regulation network. Additionally, our work will help clarify the mechanism of heterosis in rice. Further exploration of the molecular mechanism underlying the salt tolerance of CY1000 can provide a theoretical basis for breeding new salt-tolerant rice varieties.

In vivo detection of dysregulated choline metabolism in paclitaxel-resistant ovarian cancers with proton magnetic resonance spectroscopy.

BACKGROUND: Chemoresistance gradually develops during treatment of epithelial ovarian cancer (EOC). Metabolic alterations, especially in vivo easily detectable metabolites in paclitaxel (PTX)-resistant EOC remain unclear. METHODS: Xenograft models of the PTX-sensitive and PTX-resistant EOCs were built. Using a combination of in vivo proton-magnetic resonance spectroscopy (1H-MRS), metabolomics and proteomics, we investigated the in vivo metabolites and dysregulated metabolic pathways in the PTX-resistant EOC. Furthermore, we analyzed the RNA expression to validate the key enzymes in the dysregulated metabolic pathway. RESULTS: On in vivo 1H-MRS, the ratio of (glycerophosphocholine + phosphocholine) to (creatine + phosphocreatine) ((GPC + PC) to (Cr + PCr))(i.e. Cho/Cr) in the PTX-resistant tumors (1.64 [0.69, 4.18]) was significantly higher than that in the PTX-sensitive tumors (0.33 [0.10, 1.13]) (P = 0.04). Forty-five ex vivo metabolites were identified to be significantly different between the PTX-sensitive and PTX-resistant tumors, with the majority involved of lipids and lipid-like molecules. Spearman's correlation coefficient analysis indicated in vivo and ex vivo metabolic characteristics were highly consistent, exhibiting the highest positive correlation between in vivo GPC + PC and ex vivo GPC (r = 0.885, P < 0.001). These metabolic data suggested that abnormal choline concentrations were the results from the dysregulated glycerophospholipid metabolism, especially choline metabolism. The proteomics data indicated that the expressions of key enzymes glycerophosphocholine phosphodiesterase 1 (GPCPD1) and glycerophosphodiester phosphodiesterase 1 (GDE1) were significantly lower in the PTX-resistant tumors compared to the PTX-sensitive tumors (both P < 0.01). Decreased expressions of GPCPD1 and GDE1 in choline metabolism led to an increased GPC levels in the PTX-resistant EOCs, which was observed as an elevated total choline (tCho) on in vivo 1H-MRS. CONCLUSIONS: These findings suggested that dysregulated choline metabolism was associated with PTX-resistance in EOCs and the elevated tCho on in vivo 1H-MRS could be as an indicator for the PTX-resistance in EOCs.

MRI-Based Multiple Instance Convolutional Neural Network for Increased Accuracy in the Differentiation of Borderline and Malignant Epithelial Ovarian Tumors.

BACKGROUND: Preoperative differentiation of borderline from malignant epithelial ovarian tumors (BEOT vs. MEOT) is challenging and can significantly impact surgical management. PURPOSE: To develop a multiple instance convolutional neural network (MICNN) that can differentiate BEOT from MEOT, and to compare its diagnostic performance with that of radiologists. STUDY TYPE: Retrospective study of eight clinical centers. SUBJECTS: Between January 2010 and June 2018, a total of 501 women (mean age, 48.93 ± 14.05 years) with histopathologically confirmed BEOT (N = 165) or MEOT (N = 336) were divided into the training (N = 342) and validation cohorts (N = 159). FIELD STRENGTH/SEQUENCE: Three axial sequences from 1.5 or 3 T scanner were used: fast spin echo T2-weighted imaging with fat saturation (T2WI FS), echo planar diffusion-weighted imaging, and 2D volumetric interpolated breath-hold examination of contrast-enhanced T1-weighted imaging (CE-T1WI) with FS. ASSESSMENT: Three monoparametric MICNN models were built based on T2WI FS, apparent diffusion coefficient map, and CE-T1WI. Based on these monoparametric models, we constructed an early multiparametric (EMP) model and a late multiparametric (LMP) model using early and late information fusion methods, respectively. The diagnostic performance of the models was evaluated using the receiver operating characteristic (ROC) curve and compared to the performance of six radiologists with varying levels of experience. STATISTICAL TESTS: We used DeLong test, chi-square test, Mann-Whitney U-test, and t-test, with significance level of 0.05. RESULTS: Both EMP and LMP models differentiated BEOT from MEOT, with an area under the ROC curve (AUC) of 0.855 (95% CI, 0.795-0.915) and 0.884 (95% CI, 0.831-0.938), respectively. The AUC of the LMP model was significantly higher than the radiologists' pooled AUC (0.884 vs. 0.797). DATA CONCLUSION: The developed MICNN models can effectively differentiate BEOT from MEOT and the diagnostic performances (AUCs) were more superior than that of the radiologists' assessments. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Can we scale up a comprehensive school-based eye health programme in Zambia?

BACKGROUND: Globally, 19 million children have preventable vision impairment simply because refractive and eye health services are inaccessible to most of them. In Zambia, approximately 50,000 school children need spectacle provision. The School-based Eye Health Programme (SEHP) has been identified worldwide as a proven strategy to address childhood blindness. Given its great benefits, the Zambian government intends to scale up the programme. This scalability assessment aims to identify and evaluate the essential components of an effective SEHP, determine roles, assess existing capacities within user organisations, identify environmental facilitating and inhibiting factors, and estimate the minimum resources necessary for the scaling up and their proposed scale-up strategies. METHODS: Five elements (innovation, user organisation, resource team, environment, and strategies for horizontal and vertical scaling-up) were assessed guided by the ExpandNet-WHO Nine Steps for Developing a Scaling-Up Strategy. Literature review on proven strategies to reduce childhood blindness and the credibility of SEHP implemented in resource-limited settings, document review on the pilot project, questionnaires, and stakeholders' interviews were conducted to collect data for this assessment. Subsequently, twenty questions in the Worksheets for Developing a Scaling-up Strategy were used to report the assessment outcome systematically. RESULTS: Additional components of SEHP incorporated in Zambia's model enhanced the innovation's credibility and relevance. The resource team was relatively competent in the pilot project, and the same team will be employed during the scaling-up. Potential change in political parties, the lack of supply chain, and unstable financial support were identified as inhibiting factors. The objectives of SEHP were aligned with the National Eye Health Strategic Plan 2017-2021, which supports the institutionalisation of the SEHP into the existing School Health and Nutrition Programme. For the pace of expansion, replicating SEHP to another district rather than a province will be more realistic. CONCLUSION: Scaling up a comprehensive SEHP in Zambia is feasible if sufficient funding is available. Additionally, the pace must be adapted to the local context to ensure that every component within the SEHP is intact.

Noninvasive prediction of residual disease for advanced high-grade serous ovarian carcinoma by MRI-based radiomic-clinical nomogram.

OBJECTIVES: To develop a preoperative MRI-based radiomic-clinical nomogram for prediction of residual disease (RD) in patients with advanced high-grade serous ovarian carcinoma (HGSOC). METHODS: In total, 217 patients with advanced HGSOC were enrolled from January 2014 to June 2019 and randomly divided into a training set (n = 160) and a validation set (n = 57). Finally, 841 radiomic features were extracted from each tumor on T2-weighted imaging (T2WI) and contrast-enhanced T1-weighted imaging (CE-T1WI) sequence, respectively. We used two fusion methods, the maximal volume of interest (MV) and the maximal feature value (MF), to fuse the radiomic features of bilateral tumors, so that patients with bilateral tumors have the same kind of radiomic features as patients with unilateral tumors. The radiomic signatures were constructed by using mRMR method and LASSO classifier. Multivariable logistic regression analysis was used to develop a radiomic-clinical nomogram incorporating radiomic signature and conventional clinico-radiological features. The performance of the nomogram was evaluated on the validation set. RESULTS: In total, 342 tumors from 217 patients were analyzed in this study. The MF-based radiomic signature showed significantly better prediction performance than the MV-based radiomic signature (AUC = 0.744 vs. 0.650, p = 0.047). By incorporating clinico-radiological features and MF-based radiomic signature, radiomic-clinical nomogram showed favorable prediction ability with an AUC of 0.803 in the validation set, which was significantly higher than that of clinico-radiological signature and MF-based radiomic signature (AUC = 0.623, 0.744, respectively). CONCLUSIONS: The proposed MRI-based radiomic-clinical nomogram provides a promising way to noninvasively predict the RD status. KEY POINTS: • MRI-based radiomic-clinical nomogram is feasible to noninvasively predict residual disease in patients with advanced HGSOC. • The radiomic signature based on MF showed significantly better prediction performance than that based on MV. • The radiomic-clinical nomogram showed a favorable prediction ability with an AUC of 0.803.

MR image-based radiomics to differentiate type Ι and type ΙΙ epithelial ovarian cancers.

OBJECTIVES: Epithelial ovarian cancers (EOC) can be divided into type I and type II according to etiology and prognosis. Accurate subtype differentiation can substantially impact patient management. In this study, we aimed to construct an MR image-based radiomics model to differentiate between type I and type II EOC. METHODS: In this multicenter retrospective study, a total of 294 EOC patients from January 2010 to February 2019 were enrolled. Quantitative MR imaging features were extracted from the following axial sequences: T2WI FS, DWI, ADC, and CE-T1WI. A combined model was constructed based on the combination of these four MR sequences. The diagnostic performance was evaluated by ROC-AUC. In addition, an occlusion test was carried out to identify the most critical region for EOC differentiation. RESULTS: The combined radiomics model exhibited superior diagnostic capability over all four single-parametric radiomics models, both in internal and external validation cohorts (AUC of 0.806 and 0.847, respectively). The occlusion test revealed that the most critical region for differential diagnosis was the border zone between the solid and cystic components, or the less compact areas of solid component on direct visual inspection. CONCLUSIONS: MR image-based radiomics modeling can differentiate between type I and type II EOC and identify the most critical region for differential diagnosis. KEY POINTS: • Combined radiomics models exhibited superior diagnostic capability over all four single-parametric radiomics models, both in internal and external validation cohorts (AUC of 0.834 and 0.847, respectively). • The occlusion test revealed that the most crucial region for differentiating type Ι and type ΙΙ EOC was the border zone between the solid and cystic components, or the less compact areas of solid component on direct visual inspection on T2WI FS. • The light-combined model (constructed by T2WI FS, DWI, and ADC sequences) can be used for patients who are not suitable for contrast agent use.

Perfusion-based functional magnetic resonance imaging for differentiating serous borderline ovarian tumors from early serous ovarian cancers in a rat model.

BACKGROUND: Differentiation of borderline tumors from early ovarian cancer has recently received increasing attention, since borderline tumors often affect young women of childbearing age who desire to preserve fertility. However, previous studies have demonstrated that non-enhanced magnetic resonance imaging (MRI) sequences cannot sufficiently differentiate these tumors. PURPOSE: To investigate the value of dynamic contrast-enhanced MRI (DCE-MRI) and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in differentiating serous borderline ovarian tumors (SBOT) from early serous ovarian cancers (eSOCA). MATERIAL AND METHODS: Twenty SBOT and 20 eSOCA rat models were performed with DCE-MRI and IVIM-DWI at 3.0-T MR scanner. Qualitative and quantitative parameters of DCE-MRI were acquired and compared between two groups and correlated with the microvessel density (MVD). The receiver operating characteristic (ROC) curve analyses were conducted to determine their differentiating performances. RESULTS: SBOTs presented significantly lower values of the initial area under the enhancement curve (iAUC), volume transfer constant (Ktrans), and extracellular extravascular volume fraction (ve) (P < 0.05) and a significantly higher value of true diffusion (D) (P = 0.001) compared with eSOCAs. The diagnostic effectiveness of ve combined with D was significantly better than that of ve or Ktrans alone (P ≤ 0.039). CONCLUSION: DCE-MRI may represent a promising tool for differentiating SBOTs from eSOCAs and may not be replaced by IVIM-DWI. Combining DCE-MRI with DWI may improve the diagnostic performance of ovarian tumors.

Nurses' turnover intention in secondary hospitals in China: A structural equation modelling approach.

AIM: To identify the factors affecting nurses' turnover intention. BACKGROUND: The shortage of nurses has been a great challenge worldwide, and nurses' turnover may exacerbate the situation. METHODS: A cross-sectional study was conducted among nurses in six secondary hospitals in China. A model was constructed, and structured questionnaires were adopted to measure model variables. Structural equation modelling was used to verify the model. RESULTS: Totally, 594 valid questionnaires were collected. The final model showed an acceptable fit, and 35.0% of the total variation was explained. Nine of the ten pathways were statistically significant. The model verified the contribution of professional value, nursing practice, job stress and social support to turnover intention and their effects were mediated by job satisfaction and organisational commitment. As hypothesized, there existed a significant effect between job satisfaction and organisational commitment. Unexpectedly, job stress had a greater direct effect on turnover intention than job satisfaction and organisational commitment. CONCLUSIONS: The structural model provided a feasible model that could explain nurses' turnover intention in China. IMPLICATIONS FOR NURSING MANAGEMENT: To prevent the turnover of nurses, administrators and managers should advisably prioritize the effect of job stress, especially in hospitals with similar medical context.

MRI-Based Machine Learning for Differentiating Borderline From Malignant Epithelial Ovarian Tumors: A Multicenter Study.

BACKGROUND: Preoperative differentiation of borderline from malignant epithelial ovarian tumors (BEOT from MEOT) can impact surgical management. MRI has improved this assessment but subjective interpretation by radiologists may lead to inconsistent results. PURPOSE: To develop and validate an objective MRI-based machine-learning (ML) assessment model for differentiating BEOT from MEOT, and compare the performance against radiologists' interpretation. STUDY TYPE: Retrospective study of eight clinical centers. POPULATION: In all, 501 women with histopathologically-confirmed BEOT (n = 165) or MEOT (n = 336) from 2010 to 2018 were enrolled. Three cohorts were constructed: a training cohort (n = 250), an internal validation cohort (n = 92), and an external validation cohort (n = 159). FIELD STRENGTH/SEQUENCE: Preoperative MRI within 2 weeks of surgery. Single- and multiparameter (MP) machine-learning assessment models were built utilizing the following four MRI sequences: T2 -weighted imaging (T2 WI), fat saturation (FS), diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC), and contrast-enhanced (CE)-T1 WI. ASSESSMENT: Diagnostic performance of the models was assessed for both whole tumor (WT) and solid tumor (ST) components. Assessment of the performance of the model in discriminating BEOT vs. early-stage MEOT was made. Six radiologists of varying experience also interpreted the MR images. STATISTICAL TESTS: Mann-Whitney U-test: significance of the clinical characteristics; chi-square test: difference of label; DeLong test: difference of receiver operating characteristic (ROC). RESULTS: The MP-ST model performed better than the MP-WT model for both the internal validation cohort (area under the curve [AUC] = 0.932 vs. 0.917) and external validation cohort (AUC = 0.902 vs. 0.767). The model showed capability in discriminating BEOT vs. early-stage MEOT, with AUCs of 0.909 and 0.920, respectively. Radiologist performance was considerably poorer than both the internal (mean AUC = 0.792; range, 0.679-0.924) and external (mean AUC = 0.797; range, 0.744-0.867) validation cohorts. DATA CONCLUSION: Performance of the MRI-based ML model was robust and superior to subjective assessment of radiologists. If our approach can be implemented in clinical practice, improved preoperative prediction could potentially lead to preserved ovarian function and fertility for some women. LEVEL OF EVIDENCE: Level 4. TECHNICAL EFFICACY: Stage 2. J. Magn. Reson. Imaging 2020;52:897-904.

Role of proton MR spectroscopy in the differentiation of borderline from malignant epithelial ovarian tumors: A preliminary study.

BACKGROUND: Due to the overlapping imaging appearances between borderline and malignant epithelial ovarian tumors (EOTs), borderline EOTs often represent a diagnostic challenge on conventional MRI. Proton magnetic resonance spectroscopy (1 H-MRS) might have potential to differentiate borderline from malignant tumors. PURPOSE: To investigate the ability of 1 H-MRS to differentiate borderline from malignant EOTs. STUDY TYPE: Prospective. POPULATION: In all, 278 patients with adnexal masses. FIELD STRENGTH/SEQUENCE: 1.5 T Siemens Avanto MRI system and 1 H-MRS using a point-resolved spectroscopy sequence (PRESS). ASSESSMENT: Resonance peak integrals of the most common metabolites were analyzed and compared between the two groups. STATISTICAL TESTS: The ratios of metabolites between borderline and malignant EOTs were compared with the Mann-Whitney U-test. A receiver operating characteristic (ROC) curve was used to determine their differential diagnosis performances. RESULTS: In the solid components of borderline and malignant EOTs, the mean Cho/Cr, NAA/Cr, and NAA/Cho ratios were 4.4 ± 1.1 and 9.9 ± 2.8; 10.4 ± 3.0 and 2.2 ± 1.0; and 2.4 ± 0.7 and 0.3 ± 0.1, respectively (all P < 0.001). The sensitivity, specificity, and area under the curve (AUC) were 91%, 100%, and 0.98 for the Cho/Cr ratio; 100%, 98%, and 0.99 for the NAA/Cr ratio; and 100%, 100%, and 1.00 for the NAA/Cho ratio, respectively. In the cystic components, the mean Cho/Cr, NAA/Cr, and NAA/Cho ratios were 3.2 ± 0.8 and 5.1 ± 1.2; 9.1 ± 3.4 and 2.3 ± 1.4; and 2.9 ± 1.2 and 0.5 ± 0.4, respectively (all P < 0.001). The sensitivity, specificity, and AUC were 84%, 82%, and 0.89 for the Cho/Cr ratio; 94%, 97%, and 0.99 for the NAA/Cr ratio; and 94%, 97%, and 0.99 for the NAA/Cho ratio, respectively. DATA CONCLUSION: The NAA/Cho ratio is a reliable biomarker for differentiating borderline from malignant EOTs. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;49:1684-1693.

Diffusion kurtosis imaging for differentiating borderline from malignant epithelial ovarian tumors: A correlation with Ki-67 expression.

PURPOSE: To investigate the use of diffusion kurtosis imaging (DKI) in differentiating borderline from malignant epithelial ovarian tumors (MEOTs) and to correlate DKI parameters with Ki-67 expression. MATERIALS AND METHODS: Fifty-two consecutive patients with epithelial ovarian tumors (17 borderline epithelial ovarian tumors, BEOTs; 35 MEOTs) were prospectively evaluated using DKI with b values of 0, 500, 1000, 1500, 2000, and 2500 s/mm2 and standard diffusion-weighted imaging (DWI) with b values of 0 and 1000 s/mm2 using a 1.5T magnetic resonance imaging (MRI) unit. The kurtosis (K) and diffusion coefficient (D) from DKI and apparent diffusion coefficient (ADC) from standard DWI were measured, compared, and correlated with Ki-67 expression between the two groups. Statistical analyses were performed using the Mann-Whitney U-test, receiver operating characteristic (ROC) curves, and Spearman's correlation. RESULTS: The K value was significantly lower in BEOTs than in MEOTs (0.55 ± 0.09 vs. 0.9 ± 0.2), while the D and ADC values were significantly higher in BEOTs than in MEOTs (2.27 ± 0.35 vs. 1.39 ± 0.37 and 1.72 ± 0.36 vs. 1.1 ± 0.25, respectively) (P < 0.001). For differentiating between BEOTs and MEOTs, the sensitivity, specificity, and accuracy were 88.2%, 94.3%, and 92.3% for K value; 88.2%, 91.4%, and 90.4% for D value; and 88.2%, 88.6%, and 88.5% for ADC value, respectively. However, there were no differences in the diagnostic performances among the three parameters above (K vs. ADC, P = 0.203; D vs. ADC, P = 0.148; K vs. D, P = 0.904). The K value was positively correlated with Ki-67 expression (r = 0.699), while the D and ADC values were negatively correlated with Ki-67 expression (r = -0.680, -0.665, respectively). CONCLUSION: Preliminary findings demonstrate that DKI is an alternative tool for differentiating BEOTs from MEOTs, and is correlated with Ki-67 expression. However, no added value is found for DKI compared with standard DWI. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1499-1506.

Cytotoxic steroidal saponins from Trillium kamtschaticum.

Eight new steroidal saponins, trillikamtosides K-R (1-8), along with three known analogues, were isolated from the whole plants of Trillium kamtschaticum. Their structures were unambiguously established by interpretation of spectroscopic data (MS and NMR) and chemical methods. Compound 1 had a rare aglycone featuring a skeleton of 16-oxaandrost-5-en-3-ol-17-one, which was reported for the first time. The isolated saponins were tested for cytotoxicities against HCT116 cells, and trillikamtoside R (8) was found to show the most cytotoxic effect with an IC50 value of 4.92µM.

p21 is Responsible for Ionizing Radiation-induced Bypass of Mitosis.

OBJECTIVE: To explore the role of p21 in ionizing radiation-induced changes in protein levels during the G2/M transition and long-term G2 arrest. METHODS: Protein expression levels were assessed by western blot in the human uveal melanoma 92-1 cells after treatment with ionizing radiation. Depletion of p21 was carried out by employing the siRNA technique. Cell cycle distribution was determined by flow cytometry combined with histone H3 phosphorylation at Ser28, an M-phase marker. Senescence was assessed by senescence- associated-ß-galactosidase (SA-ß-gal) staining combined with Ki67 staining, a cell proliferation marker. RESULTS: Accompanying increased p21, the protein levels of G2/M transition genes declined significantly in 92-1 cells irradiated with 5 Gy of X-rays. Furthermore, these irradiated cells were blocked at the G2 phase followed by cellular senescence. Depletion of p21 rescued radiation-induced G2 arrest as demonstrated by the upregulation of G2/M transition kinases, as well as the high expression of histone H3 phosphorylated at Ser28. Knockdown of p21 resulted in entry into mitosis of irradiated 92-1 cells. However, cells with serious DNA damage failed to undergo cytokinesis, leading to the accumulation of multinucleated cells. CONCLUSION: Our results indicated that p21 was responsible for the downregulation of G2/M transition regulatory proteins and the bypass of mitosis induced by irradiation. Downregulation of p21 by siRNA resulted in G2-arrested cells entering into mitosis with serious DNA damage. This is the first report on elucidating the role of p21 in the bypass of mitosis.

[Effects of sanguisorba tannins and saponins compatibility on pharmacokinetic parameters of catechin, epicatechin and ziyuglycoside â in rats].

To study the effects of sanguisorba tannins and saponins compatibility at different proportions [tannins-saponins (1∶1) and tannins-saponins(8∶1)] after intragastric administration (50 mg•kg⁻¹) on pharmacokinetic parameters of catechin, epicatechin and ziyuglycoside Ⅰ in rats by using pharmacokinetic techniques and methods. Kinetica 5.0 software was used to calculate the pharmacokinetic parameters. The results showed that the specificity, linearity, recovery rate, precision and stability of the established detection method were in line with the test requirements. When the sanguisorba tannins and eaponins were combined at the rate of 1∶1, Vd and CL of catechin and epicatechin were increased significantly（P<0.05); MRT was significantly shortened(P<0.05); Cmax and AUC were significantly reduced(P<0.05). When the sanguisorba tannins and saponins were combined at the rate of 8∶1, Vd and CL of catechin and epicatechin were significantly reduced(P<0.05); MRT was significantly prolonged(P<0.05); Cmax and AUC were increased significantly(P<0.05). In addition, with the increase in proportion of sanguisorba tannins in the compatibility, Cmax and AUC of ziyuglycoside Ⅰ were increased significantly(P<0.05); Vd and CL were significantly reduced(P<0.05), Tmax was obviously lagging behind, and MRT was also significantly prolonged(P<0.05). In our present study, catechin, epicatechin and ziyuglycoside Ⅰ showed good pharmacokinetic behavior in rats when sanguisorba tannins and saponins were combined at the rate of 8∶1 in compatibility, which could be used as a reference for the proportion in sanguisorba tannins and saponins compatibility.

Needs and views on eye health and women's empowerment and theory of change map: implication on the development of a women-targeted eyecare programme for older Zanzibari craftswomen.

OBJECTIVES: To assess needs and views regarding eye health and empowerment from craftswomen's perspectives to develop a theory of change (ToC) for a women-targeted eyecare programme. MATERIAL AND METHODS: Eighteen stakeholders participated in a 2-day consultation workshop in Zanzibar. The composition was (1) 15 women and 3 men; (2) Unguja (n=8), Pemba (n=6) and Tanzania mainland (n=4) and (3) craftswomen (n=14) and governmental stakeholders (n=4). Thematic analysis determined the craftswomen's needs and views regarding eye health and empowerment and subsequently inputs, activities, outputs, outcomes and impact to develop the programme's initial ToC. In refining the initial ToC, we used insights from a qualitative study suggesting that improved near vision is perceived by craftswomen as a potential source of empowerment across economic, psychological, social, political and educational dimensions. RESULTS: The eye conditions experienced by the craftswomen were eye irritation caused by foreign bodies, the need for near spectacles and other eye morbidities. They were advised by the cooperatives to visit eye health centres for treatment. The main barriers to accessing services were inaccessibility and unaffordability of eye services and a lack of eye health knowledge and practices. Nineteen subthemes on women empowerment (economic n=4, social n=4, psychological n=6, education n=2 and political n=3) were obtained. We created a ToC on how investing in improving craftswomen near vision could achieve empowerment. CONCLUSION: The participants provided insights into their needs and how they would like the eyecare programme to be implemented and how they see they could be empowered in the process.

Comparison of MRI features among squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma, usual-type endocervical adenocarcinoma and gastric adenocarcinoma of cervix.

OBJECTIVE: To compare and explore the characteristics of squamous cell carcinoma (SCC), adenocarcinoma (AC) and adenosquamous carcinoma (ASC), usual-type endocervical adenocarcinoma (UEA) and gastric adenocarcinoma (GAC) of cervix. MATERIALS AND METHODS: A total of 728 cervical cancers (254 cases of AC, 252 cases of ASC, and 222 cases of SCC) confirmed by histopathology were retrospectively reviewed. Among AC, 119 UEA and 47 GAC were included. Clinical baseline data and tumor morphological features on MRI (including tumor location, shape, diameter and volume, margin, growth pattern, presence of fluid component or cyst, heterogenous and peritumoral enhancement) of all cases were collected and analyzed. The signal intensity (SI) of tumor and gluteus maximus muscle were measured and their ratios (SIR) were calculated based on T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) and contrast-enhanced T1WI at arterial and delay phases (A/DCE-T1WI). These clinical and MRI features were compared between SCC, AC and ASC, UEA and GAC, and the specific ones of each subtype were identified. RESULTS: There was a significant difference in SCC-Ag, CA-199, CEA, ADC value, SIR-DWI, presence of intratumor cyst and peritumoral enhancement between AC and ASC; in patient age, menopausal status, International Federation of Gynecology and Obstetrics (FIGO) stage, SCC-Ag, CA-125, CA-199, CEA, tumor shape, growth pattern, margin, presence of intratumor fluid component and cyst, tumor diameter and volume, ADC value, SIR-T1WI, SIR-T2WI, and SIR-DWI between SCC and AC, as well as SCC and ASC. Also, there was a significant difference in deep stromal invasion (DSI), peritumoral and heterogenous enhancement between SCC and AC, and in SIR-ACE-T1WI between SCC and ASC. There was a significant difference in reproductive history, menopausal status, FIGO stage, CA-199, DSI, lymph node metastasis (LNM), parametrial invasion (PMI), tumor location, shape, margin, growth pattern, presence of fluid component and cyst, tumor diameter and volume, SIR-T1WI, SIR-DWI, and heterogenous enhancement between GAC and UEA. CONCLUSION: The clinical and MRI features with significant differences among SCC, AC and ASC, and between UEA and GAC, can help to identify each subtype of cervical cancer.