bluuebunny/crossref_metadata_2025 huggingface dataset:
Alveolar Soft Part Sarcoma: Progress Toward Improvement in Survival? A Population-Based Study
Authors: Fujiwara Tomohiro , Nakata Eiji , Kunisada Toshiyuki , Ozaki Toshifumi , Kawai Akira
Published: October 2021

Background: Alveolar soft part sarcoma (ASPS) is a rare histological subtype of soft-tissue sarcoma, which remains refractory to conventional cytotoxic chemotherapy. We aimed to characterize ASPS and investigate whether the oncological outcome has improved over the past decade.Methods: One hundred and twenty patients with newly diagnosed ASPS from 2006 to 2017 were identified from the Bone and Soft-Tissue Tumor Registry in Japan. The Kaplan–Meier estimate and Cox proportional hazard model were used to investigate the survival outcomes and factors affecting prognosis.Results: The study cohort comprised 34 (28%) patients with localized ASPS and 86 (72%) with metastatic disease at presentation. The 5-year disease-specific survival (DSS) was 68% for all patients and 86% and 62% for localized and metastatic disease, respectively (p = 0.019). Metastasis at presentation was the only adverse prognostic factor for DSS (hazard ratio [HR]: 7.65; p = 0.048). Patients who were >25 years (80%; p = 0.023), had deep-seated tumors (75%; p = 0.002), and tumors >5 cm (5–10 cm, 81%; >10 cm, 81%; p < 0.001) were more likely to have metastases at presentation. In patients with localized ASPS, adjuvant chemotherapy or radiotherapy did not affect survival, and 13 patients (45%) developed distant metastases in the lung (n = 12, 92%) and brain (n = 2, 15%). In patients with metastatic ASPS (lung, n = 85 [99%]; bone, n = 12 [14%]; and brain n = 9 [11%]), surgery for the primary or metastatic site did not affect survival. The use of pazopanib significantly prolonged survival in patients who received systemic treatment (p = 0.045), whereas doxorubicin-based cytotoxic chemotherapy did not. Overall, a trend toward improved DSS for metastatic ASPS has been observed since 2012 (5-year, 58%–65%; p = 0.117), when pazopanib was approved for use in advanced disease.Conclusion: The national study confirmed a unique feature of ASPS with frequent metastasis to the lung and brain but an indolent clinical course. An overall trend toward prolonged survival after the introduction of targeted drugs encourages continuous efforts to develop novel therapeutic options for this therapeutically resistant soft-tissue sarcoma.
EPC-EXs Improve Neuronal Survival and Oxidative Stress Through Different Uptaking Pathways in Diabetic Hypoxia Condition
Authors: Halurkar Manasi Suchit , Wang Jinju , Chen Shuzhen , Bihl Ji
Published: October 2021

Background: Hyperglycemia contributes to cardiovascular complications in patients with type 2 diabetes. We confirmed that high glucose (HG) induces endothelial dysfunction and cerebral ischemic injury is enlarged in diabetic mice. Stem cell-released exosomes have been shown to protect the brain from ischemic stroke. We have previously shown that endothelial progenitor cells (EPCs)-released exosomes (EPC-EXs) can protect endothelial cells from hypoxia/reoxygenation (H/R) and HG-induced injury. Here, we aim to investigate the effects of EPC-EXs on astrocytes under H/R and HG-induced injury and whether miR-126 enriched EPC-EXs (EPC-EXsmiR126) have enhanced efficacy. Methods: EPC-EX uptake and co-localization were measured by fluorescent microscopy using PKH26 and DAPI staining. miR-126 enrichment was achieved by transfecting with miR-126 mimics and quantified with real-time PCR. After co-incubation, cell death or apoptosis was measured by using flow cytometric analysis and LDH (Lactate Dehydrogenase) assay. Oxidative stress/ROS (reactive oxygen species) generation was measured by DHE (Dihydroethidium) staining and lipid peroxidation assay. Results: The EPC-EXs were effectively taken up by the astrocytes in a concentration as well as time-dependent manners and were co-localized within the nucleus as well as the cytoplasm. Pathway uptake inhibitors revealed that the EPC-EXs are effectively taken up by the clathrin-mediated, caveolin-dependent, and micropinocytosis via PI3K/Akt pathway. H/R and HG-induced a cell injury which could be protected by EPC-EXs evidenced by decreased cell apoptosis, cell cytotoxicity, oxidative stress, and lipid peroxidation. Moreover, miR-126 overexpression could enhance the protective effects of EPC-EXs. Conclusions: These results collectively indicate that the EPC-EXs could protect astrocytes against the HG plus H/R-induced damage.
Construction of Novel mRNA-miRNA-lncRNA Regulatory Networks Associated with Prognosis of HCV Related HCC
Authors: Ma YiQun , SHAO LISHI , SHI CHEN , WANG JIAPING
Published: October 2021

Background: Infection with hepatitis C virus (HCV) can cause hepatic fibrosis and cirrhosis, thereby significantly increasing the risk of HCC development. Many prior studies have shown that oncogenesis and cancer progression are governed by competing endogenous RNA (ceRNA) networks composed of long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs. As such, we herein sought to identify and evaluate the prognostic relevance of novel ceRNA network related to HCC associated with HCV. Methods: Differentially expressed genes (DEGs) in the GSE140845 Gene Expression Omnibus (GEO) dataset were identified using NetworkAnalyst, and were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Gene, Genome (KEGG) pathway, and Reactome analyses. In addition, a protein-protein interaction (PPI) network was generated, and key hub genes were detected. Hub gene expression levels, as well as those of their upstream lncRNAs and miRNAs and associated survival analyses were conducted using appropriate bioinformatics databases. Predicted target relationships were additionally used to establish putative ceRNA networks for HCV-related HCC. Results: 372 and 360 upregulated and downregulated significant DEGs were identified, respectively. Functional enrichment analyses suggested that DE-mRNAs were associated with nuclear division, the cell cycle, and ATPase activity. The top 11 genes with the greatest degree of connectivity among these DE-mRNAs were selected for subsequent prognostic evaluation. The differential expression of six of these candidate mRNAs (BUB1, BUB1B, CDC20, CDC45, CDK1, NDC80) in liver tissue was validated. After further analyses of the expression and prognostic relevance of the miRNAs and lncRNAs predicted to lie upstream of these DE-mRNAs, we identified 22 miRNAs and 4 lncRNAs significantly associated with poorer-HCV-related HCC prognosis. By combining the results of these analyses, we also identified the BUB1-hsa-miR-193a-3p-MALAT1 ceRNA sub-network as being related to the survival of these patients. Conclusion: This study providing novel insights into the mRNA-miRNA-lncRNA ceRNA network and reveals potential lncRNA biomarkers in HCV related HCC.
Eight-year Operation Status and Data Analysis of the First Human Milk Bank in East China
Authors: Hu Xiaoshan , Chu Xue , Zhang Jun , Liu Feng , Chen Xiaohui , Yu Zhangbin , Han Shuping
Published: October 2021

ObjectivesTo analyze the operation status and data over the last 8 years of operation of the first human milk bank (HMB) in East China.MethodsData related to the costs, donors, donation, pasteurization, and recipients were extracted from the web-based electronic monitoring system of the HMB for the period August 1, 2013 to July 31, 2021. ResultsOver the 8 years of operation, 1,555 qualified donors donated 7,396.5 L of qualified milk at a cost of ¥1.94 million, with the average cost per liter of donor human milk being ¥262.3. The donors were between 25 and 30 years of age, and the majority (80.1%) were primipara. All the donated milk was pasteurized and subjected to bacteriological tests before and after pasteurization: 95.4% passed the pre-pasteurization tests, and 96.3% passed the post-pasteurization tests. A total of 9,207 newborns received 5,775.2 L of pasteurized donor milk. The main reason for the prescription of donor human milk was preterm birth. As a result of continuous quality improvements, January 2016 witnessed a significant increase in the volume of qualified DHM and the number of qualified donors. However, in 2020, as a result of the restrictions related to the COVID-19 pandemic, the volume of qualified DHM and the number of qualified donors decreased. Conclusions﻿Over its 8 years of operation, our HMB has made steady quality improvements in its screening and information processes. Continuous quality improvement is on ongoing need, along with recruiting more qualified donors and collecting donor human milk for vulnerable newborns.
Early postoperative serum aspartate aminotransferase for prediction of post-hepatectomy liver failure
Authors: Vassanasiri Watoo , Rungsakulkij Narongsak , Suragul Wikran , Tangtawee Pongsatorn , Muangkaew Paramin , Mingphruedhi Somkit , Aeesoa Suraida
Published: October 2021

Background

Post-hepatectomy liver failure (PHLF) is a serious complication of hepatectomy. The current criteria for PHLF diagnosis (ISGLS consensus) require laboratory data on or after postoperative day (POD) 5, which may delay treatment for patients at risk. The present study aimed to determine the associations between early postoperative (POD1) serum aminotransferase levels and PHLF.
Methods

The medical records of patients who underwent hepatectomy at Ramathibodi Hospital from January 2008 to December 2019 were retrospectively examined. Patients were classified into PHLF and non-PHLF groups. Preoperative characteristics, intraoperative findings, and early postoperative laboratory data (serum AST, ALT, bilirubin, and international normalized ratio (INR) on POD0 to POD5) were analyzed.
Results

A total of 890 patients were included, of whom 31 (3.4%) had PHLF. Cut-off points for AST of 260 U/L and ALT of 270 U/L on POD1 were predictive of PHLF. In multivariate analysis, AST >260 U/L on POD1, ICG-R15, major hepatectomy, blood loss, and INR were independently associated with PHLF.
Conclusions

Early warning from elevated serum AST on POD1, before a definitive diagnosis of PHLF is made on POD5, can help alert physicians that a patient is at risk, meaning that active management and vigilant monitoring can be initiated as soon as possible.
A Partnership Among Local Public Health Agencies, Elementary Schools, and a University to Address Childhood Obesity: A Scalable Model of the Assess, Identify, Make it Happen Process
Authors: Ingman Benjamin C , Loecke Carla J , Belansky Elaine S
Published: October 2021

BACKGROUND: One pathway to addressing childhood obesity is through implementing evidence-based practices (EBPs) shown to promote nutrition and physical activity in K-12 school settings. AIM (Assess, Identify, Make it happen) is a strategic planning process to engage stakeholders in implementing EBPs in their K-12 schools. Local Public Health Agencies (LPHAs) are a potential partner to facilitate this process to a broader audience of rural school communities.METHODS: A process and outcome evaluation design was applied in this study to examine the extent to which LPHAs effectively implemented AIM with rural/frontier schools in comparison to university staff. Data collection included a post-meeting surveys completed by facilitators, a post-intervention interview with facilitators, a survey of school task force members at the end of the AIM process, and systematic documentation of the intervention.RESULTS:Reach. Among the 26 eligible elementary schools, 18 (69.2%) agreed to participate.Effect. In total, schools facilitated by LPHAs fully implemented an average of 4.0 changes per school, while schools facilitated by the university staff fully implemented an average of 3.7 changes.Adoption. Among the five LPHAs in the target region, all five agreed to partner on the initiative, but some agencies were unable to identify sufficient personnel to facilitate all schools in their catchment area.Implementation. · In total, 89 of 94 (94.68%) meetings scheduled by LPHA facilitators occurred. 47 of 48 (97.92%) meetings scheduled by the university staff occurred.· The university staff self-reported 93% of agenda items in the AIM process as “completely” followed while LPHA facilitators reported 41% of agenda items as “completely” followed.· Task force satisfaction with the AIM process and facilitator showed limited variance across LPHAs and university-facilitated schools.Maintenance. Of the 16 school districts that agreed to participate in the school-based version of AIM, 9 (56.25%) also participated in a district-wide version of AIM two years later.CONCLUSION: AIM is an effective process for implementing EBPs in elementary schools when facilitated by LPHAs. Effective partnerships, a nuanced approach to fidelity, scalability considerations, and the role of technical assistance and training all contributed to the successful implementation of this LPHA-Elementary school partnership.
Health Equity Impact Evaluation of New Treatments – Evidence Synthesis Methods to Overcome Data Gaps
Authors: Jansen Jeroen P
Published: October 2021

Background: Distributional cost-effectiveness analysis (DCEA) has been introduced as an extension of conventional cost-effectiveness analysis to quantify health equity impacts. Although health disparities are recognized as an important concern, the typical analyses conducted to inform health technology assessment of a new intervention do not include a formal health equity impact evaluation or DCEA. One of the reasons is that the clinical trials for new interventions frequently do not have the power or are not designed to estimate the required treatment effects for sub-populations across which you want to analyze equity. The objective of the paper is to discuss how gaps in evidence regarding equity-relevant subgroup effects for new and existing interventions can potentially be overcome with advanced Bayesian evidence synthesis methods to facilitate a credible model-based DCEA. Methods: First, the evidence needs and challenges for a model-based DCEA are outlined. Next, alternative evidence synthesis methods will be summarized, followed by an illustrative example of implementing these methods. The paper will conclude with some practical recommendations. Results: The key evidence challenges for a DCEA relate to estimating relative treatment effects due to lack of inclusion of relevant subgroups in the randomized controlled trials (RCTs), lack of access to individual patient data (IPD) for all trials, small subgroups resulting in uncertain effects, and reporting gaps. Advanced Bayesian evidence synthesis methods can help overcome evidence gaps by considering all relevant direct, indirect, and external evidence simultaneously. Methods discussed include (network) meta-analysis with shrinkage estimation, conventional (network) meta-regression analysis, multi-level (network) meta-regression analysis, and generalized evidence synthesis. For a new intervention for which only RCT evidence is available and no real-world data, estimates can be improved if the assumption of exchangeable subgroup effects or the shared or exchangeable effect-modifier assumption among competing interventions can be defended. Furthermore, formal expert elicitation is worthwhile to improve estimates. Conclusion: This paper provides an overview of advanced evidence synthesis methods that may help overcome typical gaps in the evidence base to perform model-based DCEA along with some practical recommendations. Future simulation studies are needed to assess the pros and cons of different methods for different data gap scenarios.
Willingness to Join Community-Based Health Insurance and Its Associated Factors among Households in West Gojjam Zone, North Mecha Woreda ,Amhara region, Ethiopia
Authors: Demeke Getaneh Bizuayehu
Published: October 2021

Background

Community-based health insurance schemes are becoming increasingly recognized as a potential strategy to achieve universal health coverage in developing countries. Ethiopia is a low income country with more of health spending out of pocket payment by households. Health insurance is also expected to provide financial protection because it reduces the financial risk associated with falling ill. Therefore; financial risk in the absence of health insurance is equal to the out-of-pocket expenditures because of illness.
Method

Cross-sectional community based study design was conducted by using a pretested structured questionnaire. Multi-stage cluster, simple random and systematic sampling techniques was used to select 296 households as study units which were allocated to the kebeles proportionately. The sampled households were selected using simple random sampling technique. Bivariate and multivariate logistic regression was used for analysis of variables and 95% confidence level and P value <0.05 was used to measure strength of association.
Results

A total of 296 sampled study participants, 285 participated in this study with a response rate of 96.3%.From this, (90.9%) were willing to join and (89.8%) of them were willingness to pay CBHI. the benefits of join the scheme were as follows, (86.8%) were reduce OOP expenditure, (8.3%) of them improve health status, (2.3%) were reduce the risk of severity and (2.6%) foster productivity.
Conclusions

This study showed that the proportion of willingness to join CBHI was higher than the findings of others study in the country and it is encouraging for planned strategy to expanding the scheme throughout the country. The main challenges utilization of health services in government health institutions were absence of available medicine, poor service delivery, lack of enough laboratory, health professional’s lack of good behavior and shortage of ambulance services. To alleviate such problem the government should be encourage access to health services.
Screening of Potential Biomarkers and Therapeutic Targets for T2DM-related Alzheimer's Disease Based on Bioinformatics Analysis
Authors: He Zhengqiang
Published: October 2021

More and more studies have suggested that type 2 diabetes mellitus (T2DM) was susceptible to trigger Alzheimer’s disease(AD), but the common underlying mechanism were unclear. We want to perform bioinformatic analysis with public databases. The T2DM dataset GSE95849 and AD dataset GSE97760 were selected from Gene Expression Omnibus (GEO) database. Then, we identified differentially expressed genes (DEGs) and the communal DEGs between the two diseases, which perform to the enrichment analysis, protein-protein interaction (PPI) network analysis, correlation analysis.We found 255 communal DEGs between T2DM and AD. They were enriched in negative regulation of actin filament depolymerization and regulation of actin filament depolymerization. Top 5 hub genes which identified from the PPI network were enriched in autophagy. The actin filament and autophagy may be the key association between the two diseases.
Impact of crustal deformation detection by the DSI (difference of split-band interferograms) method with PALSAR-2 data: A case study on the 2016 Kumamoto Earthquake
Authors: Ozawa Taku , Himematsu Yuji
Published: October 2021

Interferometric Synthetic Aperture Radar (InSAR) is a useful tool for detecting surface deformations at high spatial resolutions. When InSAR is applied to huge surface deformations, clear fringes with complicated phase gaps often appear in the interferograms. Although the surface deformations in such areas are important for understanding their mechanisms and for investigating disasters, it is difficult to convert the data on such fringes to surface deformation information because of difficulties associated with phase unwrapping. To resolve these difficulties, we created multiple SAR pairs with different frequencies using a band-pass filter and derived the difference of interferograms which are generated from these SAR pairs. Generally, its result corresponds to the result of SAR observations made with long-wavelength radar. Therefore, a phase wrap was less likely to occur, and phase unwrapping was easy to accomplish. We applied this method to the PALSAR-2 data pairs for the 2016 Kumamoto Earthquake and succeeded in identifying huge crustal deformations with complicated phase gaps in the vicinity of surface ruptures. Comparing these results with the crustal deformations observed from GNSS measurements, the root-mean-squares of the differences were found to be approximately 4 cm. Although this accuracy was poorer than that of conventional InSAR, it was nearly equivalent to that of the offsettracking method. Furthermore, its spatial resolution was significantly better than that of the offset-tracking method. However, the disadvantage of this method is that its detection accuracy is significantly degraded in zones with low coherence, due to noise amplification. The standard deviation of the noise component was approximately 2 cm for pixels with coherences above 0.7. However, for pixels with a coherence lower than 0.2, the standard deviation was greater than 10 cm, and the noise component occasionally exceeded 1 m. Despite the disadvantages of this method, it is effective for the detection of huge crustal deformations with high spatial resolution in areas where phase unwrapping methods for conventional InSAR are inappropriate.
Predicting the difference in treatment response and survival time of lung adenocarcinoma patients based on a prognostic risk model of glycolysis-related genes
Authors: Zhao Rongchang , Ding Dan , Ding Yan , Han Rongbo , Wang Xiujuan , Zhu Chunrong
Published: October 2021

Background

Multiple factors affect the survival time of patients with lung adenocarcinoma (LUAD). Specifically, the therapeutic effect of medicines and the disease recurrence probability differs among patients with the same stage of LUAD. Thus, effective prognostic predictors need to be identified.
Methods

Based on the tumor mutation burden (TMB) data obtained by TCGA, LUAD was divided into high and low groups, and the differentially expressed glycolysis-related genes between the two groups were screened out. Cox regression was used to obtain a prognostic model. A receiver operating characteristic (ROC) curve and calibration curve were generated to evaluate the nomogram that was constructed based on clinicopathological characteristics and the risk score. Two datasets (GSE68465 and GSE11969) from Gene Expression Omnibus (GEO) were used to verify the prognostic performance of the gene. Furthermore, differences in immune cell distribution, immune-related molecules and drug susceptibility were assessed for their relationship with the risk score.
Results

We confirmed a 5-gene signature (FKBP4, HMMR, B4GALT1, ERO1L, ENO1) capable of dividing patients into two risk groups. There was a significant difference in overall survival (OS) times between the high-risk group and the low-risk group (P = 1.085e-4), with the low-risk group having a better survival outcome. Through multivariate Cox analysis, the risk score was confirmed to be an independent prognostic factor (HR = 1.289, 95% CI = 1.202-1.383, P < 0.001), and the ROC curve and nomogram exhibited accurate prediction performance. Validation of the data obtained in the GEO database yielded similar results. Additionally, there were significant differences in cisplatin, paclitaxel, gemcitabine, docetaxel, gefitiniband erlotinib sensitivity between the low-risk and high-risk groups.
Conclusions

Our results reveal that glycolysis-related gene are feasible predictors of LUAD patient survival and response to therapeutics.
Neural Architecture Search For Skin Cancer Detection
Authors: Kandukuri Nikhil , Sakhtivel Sangeetha , Xie Pengtao
Published: October 2021

Neural Architectural Search (NAS) is a novel method capable of achieving state-of-the-art performance with limited computational resources and time. These coupled factors have resulted in its increasing popularity in many domains. NAS helps to discover an effective architecture for a given task. In parallel, learning through tests, a technique used in human learning aims at improving learning results: a chain of new assessments are conducted with increasing difficulty; the learner uses them to discover susceptible points, and those susceptible points are further addressed to pass the evaluation effectively. When applied in the case of learning in machines, this technique enhances their learning ability and is called Learning by passing tests(LPT). We propose to use the LPT technique in combination with NAS, particularly for Differentiable Architecture Search(DARTS), Progressive Differentiable Architecture Search(PDARTS) and, Partially Connected Differentiable Architecture Search(PCDARTS) to solve the medical challenge of Skin Cancer Classification. A bilevel optimization algorithm is formulated using LPT and is applied on the HAM10000 dataset and the Kaggle Skin Cancer: Malignant Vs. Benign dataset. Our LPT algorithm coupled with NAS can attain better performance than the traditional NAS methods and different state-of-the-art models for the given classification task.
Assessing the Psychometric Properties of the Chinese Return-to-Work Self-Efficacy Questionnaire Using Rasch Model Analysis
Authors: Liu Feng , Zhang Zhen-xiang , Lin Bei-lei , Ping Zhi-guang , Mei Yong-xia
Published: October 2021

Background Self-efficacy is a significant predictor of return to work and affects the confidence of survivors to return to work after illness. The Return-to-work self-efficacy (RTW-SE) questionnaire is a self-report questionnaire to assess confidence in returning to work with good reliability and validity. The aim of this study was to translate and cross-culturally adapt the RTW-SE questionnaire into Chinese and examine the psychometric properties among young and middle-aged stroke survivors using rasch model analysis.Methods The cross-cultural adaptation and translation procedures followed a dual-translation approach. The psychometric properties of the RTW-SE questionnaire were examined using Rasch model analysis by Winsteps software. The unidimensionality and local independence were analyzed by principal component analysis and standardized residual correlations. Category diagnostics were performed for scale function, and the item fit, reliability, and separation were also validated. Item-person maps were used to examine the distribution and matching of item’s difficulty and person ability. Finally, the differential item functioning (DIF) was used to measure gender-related group equivalence.Results A total of 366 participants aged 23–59 years were recruited from three communities in Zhengzhou. The RTW-SE questionnaire demonstrated unidimensionality and a 5-point Likert rating scale was more appropriate to investigate young and middle-aged stroke survivors’self-efficacy. There was a good fit for the items with both person and item reliabilities greater than 0.8 and separation indices of 3.75 and 3.94, respectively. The item difficulty was identified from the item-person map as not covering person ability, but the scale did not have an age-related DIF.Conclusions The results confirm evidence of appropriate psychometric properties of the RTW-SE questionnaire and can be used as a reliable and validated instrument for measuring self-efficacy to return to work in young and middle-aged Chinese patients with stroke.
Incidence, Mortality, Survival, and Prognostic Analysis of Epithelial Ovarian Cancer Patients in Brunei Darussalam: A Population-Based Study
Authors: Leong Elvynna , Ong Sok King , Jali Fadzilah , Naing Lin
Published: October 2021

Background

Ovarian cancer is the fifth most common cancer among females in Brunei Darussalam in 2017. This study aims to provide nationwide cancer statistics including cancer incidence, mortality, survival rates for women diagnosed with epithelial ovarian cancer, and evaluate the prognostic factors of epithelial ovarian cancer patients survival in Brunei Darussalam.
Methods

This is a retrospective population-based study of patients diagnosed with epithelial ovarian cancer between 1st January 2007 and 31st December 2017 in Brunei Darussalam. Crude, age-specific, age-standardized incidence and mortality rates per 100,000 women were calculated. Kaplan-Meier survival analysis method was used to determine the overall 5-years survival rate of epithelial ovarian cancer patients. Log-rank test was used to examine the differences in survival between groups. The Multivariable Cox Proportional Hazard (PH) regression models were used to estimate the hazard ratio (HRs) for overall survival and to identify the prognostic factor of epithelial ovarian cancer patients. PH assumption over time for these models were evaluated.
Results

A total of 207 patients were included in the study. The crude incidence and mortality rates were 9.7 and 3.6 per 100,000 respectively while the age-standardized incidence and mortality rates were 11.3 (95% CI: 9.7, 12.9) and 4.5 (95% CI: 3.4, 5.6) per 100,000 respectively in the period 2007-2017. The overall mean age at diagnosis was 48.4 (standard deviation=15.3) years. The overall survival rates at 1, 3, and 5 years for epithelial ovarian cancer patients were 79.7%, 69.7%, and 61.4% respectively. Age at diagnosis, district, cancer stage, and histology were the significant prognostic factors for epithelial ovarian cancer patients’ survival. Older age at diagnosis (\(\ge\)70 years vs <40 years), regional or advanced stage (vs localized stage) and having undifferentiated or other epithelial ovarian (vs serous carcinoma) were associated with having higher hazard of death while patients residing in Belait district (vs Brunei Muara) was associated with having lower hazard.
Conclusion

More efforts and research should be made to detect the disease at early stage through education and public awareness to ensure the availability of high-quality care for all women with ovarian cancer and to improve the survival rates of patients with ovarian cancer.
A Retrospective Analysis of the Correlation between Trichomonas Vaginalis Infection and Infertility
Authors: Zhang Zhenchao , Li Yuhua , Lu Haoran , Li Dongxian , Zhang Rui , Xie Xianghuan , Guo Lihua , Hao Lixia , Tian Xiaowei , Yang Zhenke , Wang Shuai , Mei Xuefang
Published: October 2021

Background: Trichomonas vaginalis (T. vaginalis) is an extracellular flagellated protozoan parasitizing the human genital and urinary tracts. T. vaginalis infection impacts human reproductive function, but whether it causes infertility is still a matter of debate.Methods: In this work, we consulted 237 relevant articles, which were classified into three categories: epidemiological investigations (104), review articles (40), and research articles (62). RevMan 5.4 was used to conduct a meta-analysis of the articles reporting epidemiological investigations comparing the incidence of T. vaginalis infection between infertile and fertile groups.Results: The results indicated that rate of T. vaginalis infection in the infertile group was lower than that in the fertile group. However, an epidemiological survey showed that the infertility rate of population infected with T. vaginalis was significantly higher than that of population without T. vaginalis infection. Most review articles stated that T. vaginalis infection causes infertility, while a small fraction of these articles were inconclusive. The conclusion that T. vaginalis infection can lead to infertility is supported by the research articles, which indicated the main pathogenic mechanisms are as follows: T. vaginalis impairs sperm quality, resulting in infertility; the immune response triggered by T. vaginalis infection impacts human reproductive function; and T. vaginalis impairs ovum quality, resulting in infertility.Conclusion: Our study confirmed that T. vaginalis infection can lead to infertility and provides a foundation for further investigations into its pathogenesis.
Predictors of Poor Quality of Life among People Living with HIV/AIDS on Antiretroviral therapy in Jimma zone Public Hospitals, South West Ethiopia: A Mixed-method Study.
Authors: Gesese Abreha Addis
Published: October 2021

Background: Given the benefits of ART (Antiretroviral Therapy) for people living with HIV/AIDS, their quality of life continues to impair. Moreover, several studies have been investigated the magnitude of quality of life among developed countries with a paucity of behavioral and psychosocial factors. Thus, the objective of this study was to identify predictors of poor quality of life among people living with HIV on ART in Jimma Zone Public Hospitals, Southwest Ethiopia. Methods: Institution-based case-control study triangulated with a qualitative method was employed. The sample size was determined using Epi-info 7.1.1 using the ratio of 1:3 cases to controls. A simple random sampling technique was conducted to select cases and controls. Data were entered into Epi-Data and analyzed using SPSS version 20. Qualitative data were collected from purposely selected key informants and analyzed manually. The study was conducted from March 10 to April 30, 2018.Results: a total of 81(25.1%) cases and 242(75.9%) controls were included in the study. Those PLWHA who chew Khat occasionally (AOR: 4.3; 95% CI: 1.01,17.8) and at weakly intervals (AOR: 6.3, 95% CI:2.0, 20.7), Stigmatism(AOR: 9.2; 95% CI:3.5, 24.3), severe depression(AOR: 16.1; 95% CI:5.2, 49.6), fair baseline ART adherence (AOR: 10.4; 95% CI:2.4, 44.8), poor baseline ART adherence (AOR: 6.4;95% CI:2.0,20.7), baseline WHO stage III, IV(AOR4.9,95%CI:2.0,11.5), current WHO stage III,IV (AOR: 3.9; 95% CI: 1.1, 13.5), current BMI <18.5 kg/m2 (AOR 2.37 95% CI (1.00, 5.62) and recent low hemoglobin level <12.8 mg/dl (AOR: 4.1; 95% CI:1.7, 9.7) were independently associated with poor quality of life. Key informant interviews identified that financial and food insecurity, stigma and discrimination, poor adherence, and side effect were the predictors that affect the quality of life.Conclusion: Multiple predictors of poor quality of life have been identified from the quantitative and key informant interviews. Khat chewing frequency (occasionally and weekly), stigma, depression, baseline drug adherence, duration on ART(less than 36 months), baseline WHO stage III/IV, Current WHO III, IV, being underweight in the current BMI, most recent hemoglobin level below 12.8mg/dl, including financial and food insecurity, stigma and discrimination, poor adherence and side effect from key informant interview. Therefore, effective interventions should be targeted by incorporating responsible bodies towards boosting the quality of life of PLWHIV by emphasizing avoiding behavioral factors like khat chewing, alcohol, shisha. Counseling and guidance on treatment adherence and follow-up should be done. Continuous awareness creation, dietary diversity, and modifications and guide on income-generating activities.
Fear of COVID-19, Internet Addiction, Learning Burnout, and Psychological Health On Teenagers in China at Post-Pandemic Era: A Serial Mediation Model
Authors: Hu Rui , Ye Maolin , Lai Bingbing , Luo Fen , Yang Minyi , Yuan Jinua , Tao QIan
Published: October 2021

Background: The 2019 coronavirus disease (COVID-19) pandemic produces a long-term effect on adolescent psychological health. There were two objectives of this study: (1) To compare psychological outcomes between an early stage of pandemic and post-pandemic era among junior high and high school students in China; (2) To investigate how COVID-19 fear impacts psychological health through a serial mediation of Internet addiction and learning burnout.Methods: Two cross-sectional online surveys were conducted among Chinese adolescents at April 2020 and at April 2021, respectively. Psychological consequence was assessed by the Depression, Anxiety and Stress Scale (DASS-21). In addition, influencing factors were assessed by the Fear of COVID-19 scale (FCV-19S), Internet Addiction Test (IAT), and Maslach Burnout Inventory-Student Survey (MBI-SS).Results: Our sample comprised 501 junior high school students and 540 high school students. There was a significant increase in symptoms of depression (χ2 = 7.03, P < 0.01), anxiety (χ2 = 35.50, P < 0.01), and stress (χ2 = 13.60, P < 0.01) at post-pandemic era compared with an early stage of COVID-19. Importantly, Internet addiction and learning burnout were identified the serial mediators between fear of COVID-19 and psychological health (β = 0.02, 95% CI = 0.01, 0.03).Conclusions: During the post-pandemic era in China, an increased number of junior high and high school students' psychological health was affected compared with the number during the pandemic. Furthermore, fear of COVID-19 influenced psychological health through first Internet addiction and then learning burnout.
Joint Genome-Wide Association Study Identifies Twenty-One Novel Loci for Age at Menarche and Highlights Its Causal Association with Other Complex Diseases
Authors: Feng Gui-Juan , Xu Qian , Ni Jing-Jing , Yang Shan-Shan , Han Bai-Xue , Wei Xin-Tong , Zhang Hong , Zhao Qi-Gang , Zhang Lei , Pei Yu-Fang
Published: October 2021

Age at menarche (AAM) is a sign of puberty of females. It is a heritable trait associated with various adult diseases. However, the genetic mechanism that determines AAM and links it to disease risk is poorly understood. Aiming to uncover the genetic basis for AAM, we conducted a joint association study in up to 438,089 participants from 3 genome-wide association studies of European and East Asian ancestries. Twenty-one novel genomic loci were identified at the genome-wide significance level. Besides, we observed significant genetic correlations between AAM and 67 complex traits, and the highest genetic correlation was observed between AAM and body mass index (rg=-0.19, P=6.11×10−31). Latent causal variable analyses demonstrate that there is a genetically causal effect of AAM on high blood pressure (GCP=0.47, P=0.02), forced vital capacity (GCP=0.63, P=0.02), age at first live birth (GCP=0.51, P=0.03), impedance of right arm (GCP=0.41, P<1×10-7) and right leg fat percentage (GCP=-0.10, P=0.02), etc. Enrichment analysis identified 5 enriched tissues and 51 enriched gene sets. Four of the five enriched tissues were related to the nervous system, including the hypothalamus middle, hypothalamo hypophyseal system, neurosecretory systems and hypothalamus. The fifth tissue was the retina in the sensory organ. The most significant gene set was the ‘decreased circulating luteinizing hormone level’ (P=2.45×10-6). Our findings may provide useful insights that elucidate the mechanisms determining AAM and the genetic interplay between AAM and some traits of women.
Tacrolimus Significantly Improved the Outcome of CIDP Patients With Autoantibodies Against Paranodal Proteins
Authors: Yang Meng-ge , Ji Suqiong , Xu Li , Gao Huajie , Zhang Qing , Bu Bitao
Published: October 2021

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated disabling neuropathy. CIDP with antibodies against the paranodal proteins has a low prevalence, poor prognosis and treatment difficulty. Moreover, there is currently a lack of data on the application of immunosuppressive agents. In this retrospective observational study, we aimed to evaluated the response to tacrolimus (a immunosuppressor with high efficacy) in CIDP with autoantibodies against paranodal proteins by reviewing 5 patients received daily tacrolimus. One patient started tacrolimus treatment at the first episode and eventually achieved full clinical remission without relapse. Four patients experienced worsening during corticosteroids tapering. They gradually improved after adding oral tacrolimus except one patient relapsed again due to tacrolimus discontinuation. Moreover, 3 patients were successfully withdrawn from corticosteroids and 2 patients took corticosteroids at low maintenance dose (10mg/d) after tacrolimus treatment. Furthermore, decreased nerve conduction velocity and action potential amplitudes gradually returned to a normal level after tacrolimus and corticosteroids treatment. In conclusions, tacrolimus significantly improved the outcome of CIDP patients with autoantibodies against paranodal proteins by preventing relapses, reducing corticosteroids dependence and enhancing nerve repair. Combination therapy with corticosteroids and tacrolimus may be an effective therapeutic regimen.
HAT2 CH2 Score Performance Predicting Neurologic Events After Cardiac Implantable Electronic Device
Authors: Chen Ju-Yi , Chen Tse-Wei , Lu Wei-Da
Published: October 2021

The HAT2CH2 score has been evaluated for predicting new-onset atrial fibrillation in several clinical conditions, but never for adverse neurologic events. We aimed to evaluate the effectiveness of HAT2CH2 score in predicting neurologic events in patients with cardiac implantable electronic device (CIED), comparing with atrial high-rate episodes (AHRE). This case-control study enrolled 314 consecutive patients aged 18 years or older with CIED implantation between January 2015 and April 2021. Patient data were analyzed retrospectively. The primary endpoint was subsequent neurologic events (NE) after implantation. AHRE was defined as > 175 bpm (Medtronic®) lasting ≥ 30 seconds. Variables associated with independent risk of NE were identified using multivariate Cox regression analysis with time-dependent covariates. Patients’ median age was 73 years and 61.8% of them were male. During follow-up (median 32 months), 18 NE occurred (incidence rate 2.15/100 patient-years, 95% CI 1.32-4.30). Multiple Cox regression analysis showed that the HAT2CH2 score (HR 2.972, 95% CI 2.143-4.123, p < 0.001) was an independent predictor for NE. Optimal HAT2CH2 score cutoff value was 3 with highest Youden index (AUC, 0.923; 95% CI, 0.881–0.966; p < 0.001). Significant increase was observed in NE occurrence rates using the HAT2CH2 score (p < 0.001). The HAT2CH2 score and episodes of AHRE lasting ≥ 1 minute are independent risk factors for NE in patients with CIED.
Therapeutic Targeting of Histone Lysine Demethylase KDM4B Blocks the Growth of Castration-resistant Prostate Cancer
Authors: Duan Lingling , Chen Yu-An , Liang Yanping , Chen Zhenhua , Lu Jun , Fang Yong , Cao Jiazheng , Lu Jian , Zhao Hongwei , Pong Rey-Chen , Hernandez Elizabeth , Kapur Payal , Tran Tram Anh T , Smith Tristan , Martinez Elisabeth D. , Ahn Jung-mo , Hsieh Jer-Tsong , Luo Junhang , Liu Zhi-Ping
Published: October 2021

Background: Accumulating evidence points to epigenetic mechanisms as essential in tumorigenesis. Treatment that targets epigenetic regulators is becoming an attractive strategy for cancer therapy. The role of epigenetic therapy in prostate cancer (PCa) remains elusive. Previously we demonstrated a correlation of levels of histone lysine demethylase KDM4B with the appearance of castration resistant prostate cancer (CRPC) and identified a small molecular inhibitor of KDM4B, B3. In this study, we aim to define the role of KDM4B in promoting PCa progression and test the efficacy of B3 using clinically relevant PCa models. Methods: KDM4B was overexpressed in LNCaP cells or knocked down (KD) in 22Rv1 cells. The specificity of B3 was determined in vitro using recombinant KDM proteins and in vivo using 22Rv1 cell lysates. The efficacy of B3 monotherapy or in combination with androgen receptor (AR) antagonist enzalutamide or the mTOR inhibitor rapamycin was tested using xenograft models in castrated mice. Comparative transcriptomic analysis was performed on KDM4B KD and B3-treated 22Rv1 cells to determine the on-target (KDM4B-dependent) and off-target (non-KDM4B-associated) effects of B3.Results: Overexpression of KDM4B in LNCaP cells enhanced its tumorigenicity whereas knockdown of KDM4B in 22Rv1 cells reduced tumor growth in castrated mice. B3 suppressed the growth of both 22Rv1 and VCaP xenografts and sensitized 22Rv1 cells to enzalutamide inhibition. B3 also inhibited 22Rv1 tumor growth synergistically with rapamycin that resulted in cell apoptosis. Mechanistically, B3 inhibited expression of AR-V7 and genes involved in epithelial-to-mesenchymal transition. DNA replication stress marker γH2A.X was upregulated by B3, which is further increased when combined with rapamycin. Based on transcriptomic and biochemical analyses, B3 inhibits both H3K9me3 and H3K27me3 demethylase activity, which is believed to underlie its anti-tumor action.Conclusions: Our studies establish KDM4B as a potent target for CRPC and B3 as a potential therapeutic agent. B3 as monotherapy or in combination with other anti-PCa therapeutics offers proof of principle for the clinical translation of epigenetic therapy targeting KDMSs for CRPC patients.
Stabile SERS Encoded Silver Silica Nanocomposites for Industrial Labeling – the Case of COVID-19 Diagnosis
Authors: Xiao Can , de Simón Bernat Mir , Gil Pilar Rivera
Published: October 2021

Biosensors, especially those with a SERS readout, are required for an early and precise healthcare diagnosis. Unreproducible SERS platforms hampers the clinical translation of SERS. Here we report a synthetic procedure to obtain stabile, reproducible and robust highly-SERS performing nanocomposites for labelling. We control the NPs agglomeration and codification which results in an increased number of hot spots, thus exhibiting reproducible and superior Raman enhancement. We studied fundamental aspects affecting the plasmonic thiol bond resulting in pH exhibiting a determining role. We validated their biosensing performance by designing a SERS-based sandwich immunoassay against COVID-19. The limits of detection for the recombinant SARS-CoV-2 protein is below 0.01 ng/μL. We offered herein one nanostructure with robust and homogeneous SERS signal which can be potentially applied for biodiagnosis.
Study On Cutting Force and Tool Vibration For Optimization of Depth of Cut in Ultra-Precision Planing Process of the Master Mold For Retro-Reflection Film
Authors: Jeong Ji-Young , Han Jun Sae , Gwak Eun-Ji , Choi Doo-Sun , Je Tae-Jin
Published: October 2021

The micro-triangular pyramid patterns are widely used in advanced optical components with retro-reflection characteristic. The performance of the retro-reflection is affected by an effective area, and it can be maximized by machined surface without defects such as edge blunt, burr, surface roughen. The ultra-precision planing process is well-known that can fabricate superior surface when the depth of cut (DOC) is applied to minimum depth above the critical value to prevent the size effect. However, it was very difficult to determine a DOC without comparing of quality of machined surfaces through the ultra-high magnification measuring instrument such as SEM. In this study, the critical DOC which is key parameter was analyzed using cutting force and tool vibration signals. These signals were converted to specific cutting resistance and frequency spectrum, respectively. As a result, spectrum frequency signal was more effective and accurate than specific cutting energy, and critical DOC was determined to 1µm. This proposed process was validated by comparing the quality variation of the machined surfaces with analysis result based on cutting signals. Finally, a master mold with area of 250mm2 for fabrication of the retro-reflection film was manufactured by applying optimized DOC, and the retro-reflection film was fabricated by press molding process. This retro-reflection film was clearly recognized at a distance of 100m from light source with low power.